Sarah Dunlop

Impaired binocular vision after unilateral optic nerve regeneration in the frog Litoria moorei

Publisher: Elsevier BV

Date: 03-1997

DOI: 10.1016/S0166-4328(96)00150-7

Abstract: Behavioural responses to objects in the binocular field were examined in frogs with one regenerate and one intact optic nerve. Data were compared to those for normal controls and for frogs with vision via one intact optic nerve. During prey acquisition, frogs with regenerated optic nerves underestimated the distance to the prey on their first strike as a consequence, the regenerate series made several attempts to achieve a successful prey capture. By contrast, normal frogs and those using only one eye struck accurately at the prey and usually captured it on the first attempt. However, frogs using only one eye struck from a closer distance than either the regenerate or normal series. Frogs with regenerated optic nerves also made more errors than either of the other series when leaping through a set of closely spaced horizontally aligned rods. Our results show that prey capture and the negotiation of horizontally aligned rods is impaired in animals using one regenerated and one intact optic nerve as compared to both normal frogs and those using only one eye. We suggest that the poor visual performance for frogs with one regenerated and one intact optic nerve for tasks presented in the binocular field is related to the integration of a degraded and a normal image within the visual centres.

Continued neurogenesis is not a pre-requisite for regeneration of a topographic retino-tectal projection

Publisher: Elsevier BV

Date: 06-2001

DOI: 10.1016/S0042-6989(01)00053-0

Abstract: Electrophysiological recording demonstrated that visuo-tectal projections are topographically organised after optic nerve regeneration in aged Xenopus laevis. 3H-thymidine autoradiography confirmed previous reports [Taylor, Lack, & Easter, Eur. Journal of Neuroscience 1 (1989) 626-638] that cell ision had already ceased at the retinal ciliary margin. The results demonstrate that, contrary to a previous suggestion [Holder & Clarke, Trends in Neuroscience 11 (1988) 94-99], continued neurogenesis is not a pre-requisite for the re-establishment of appropriate connections with target cells.

Repeated prenatal corticosteroids reduce glial fibrillary acidic protein in the ovine central nervous system

Publisher: Walter de Gruyter GmbH

Date: 03-01-2002

DOI: 10.1515/JPM.2002.029

Differential responses to increasing numbers of mild traumatic brain injury in a rodent closed‐head injury model

Publisher: Wiley

Date: 27-03-2019

DOI: 10.1111/JNC.14673

Abstract: Following mild traumatic brain injury (mTBI), further mild impacts can exacerbate negative outcomes. To compare chronic damage and deficits following increasing numbers of repeated mTBIs, a closed-head weight-drop model of repeated mTBI was used to deliver 1, 2 or 3 mTBIs to adult female rats at 24 h intervals. Outcomes were assessed at 3 months following the first mTBI. No gross motor, sensory or reflex deficits were identified (p > 0.05), consistent with current literature. Cognitive function assessed using a Morris water maze revealed chronic memory deficits following 1 and 2, but not 3 mTBI compared to shams (p ≤ 0.05). Oxidative damage to DNA was assessed immunohistochemically in the dentate hilus of the hippoc us and splenium of the corpus callosum no changes were observed. IBA1-positive microglia were increased in size in the cortex following 1 mTBI and in the corpus callosum following 2 mTBI compared to shams (p ≤ 0.05) no changes were observed in the dentate hilus. Glial fibrillary acidic protein (GFAP)-positive astrocyte immunoreactivity was assessed in all three brain regions and no chronic changes were observed. Integrity of myelin ultrastructure in the corpus callosum was assessed using transmission electron microscopy. G ratio was decreased following 2 mTBIs compared to shams (p ≤ 0.05) at post hoc level only. The changing patterns of damage and deficits following increasing numbers of mTBI may reflect dynamic responses to small numbers of mTBIs or a conditioning effect such that increasing numbers of mTBIs do not necessarily result in worsening pathology. OPEN SCIENCE BADGES: This article has received a badge for *Open Materials* because it provided all relevant information to reproduce the study in the manuscript. The complete Open Science Disclosure form for this article can be found at the end of the article. More information about the Open Practices badges can be found at cos.io/our-services/open-science-badges/. Cover Image for this issue: doi: 10.1111/jnc.14508.

Retinal maturation is delayed by repeated, but not single, maternal injections of betamethasone in sheep

Publisher: Springer Science and Business Media LLC

Date: 2000

DOI: 10.1038/EYE.2000.20

Abstract: The safety and efficacy of prescribing a single maternal course of corticosteroid during pregnancy has been documented in human trials. However, the current trend is to prescribe repeated courses of corticosteroid. We investigated an aspect of the safety of this practice in an animal model. Date-mated ewes received saline, single or four corticosteroid injections between days 104 and 124 of gestation (term = 150). Lambs were delivered on day 125 or 145 by caesarian section after spinal anaesthesia. Eye diameters were measured and semi-thin toluidine-blue-stained transverse sections of retinae were analysed using an Optimus Image Analysis program. At 125 days, retinal measures in the ventral periphery and area centralis were significantly thinner than control (p = 0.0001). At 145 days, total eye size was significantly reduced compared with control (p = 0.03), and retinal measures in the ventral periphery (p = 0.0001), but not the area centralis (p = 0.19), remained significantly different from control. Repeated maternal administration of corticosteroid may affect retinal maturation in the fetus.

An Unexpected Transient Breakdown of the Blood Brain Barrier Triggers Passage of Large Intravenously Administered Nanoparticles

Publisher: Springer Science and Business Media LLC

Date: 04-03-2016

DOI: 10.1038/SREP22595

Abstract: The highly restrictive blood-brain barrier (BBB) plays a critically important role in maintaining brain homeostasis and is pivotal for proper neuronal function. The BBB is currently considered the main limiting factor restricting the passage of large (up to 200 nm) intravenously administered nanoparticles to the brain. Breakdown of the barrier occurs as a consequence of cerebrovascular diseases and traumatic brain injury. In this article, we report that remote injuries in the CNS are also associated with BBB dysfunction. In particular, we show that a focal partial transection of the optic nerve triggers a previously unknown transient opening of the mammalian BBB that occurs in the visual centres. Importantly, we demonstrate that this transient BBB breakdown results in a dramatic change in the biodistribution of intravenously administered large polymeric nanoparticles which were previously deemed as BBB-impermeable.

Transient up-regulation of the rostrocaudal gradient of ephrin A2 in the tectum coincides with reestablishment of orderly projections during optic nerve regeneration in goldfish

Publisher: Elsevier BV

Date: 11-2000

DOI: 10.1006/EXNR.2000.7486

Multimodal analysis of PEI-mediated Endocytosis of Nanoparticles in Neural Cells

Publisher: American Chemical Society (ACS)

Date: 27-10-2011

DOI: 10.1021/NN2022149

Abstract: Polymer nanoparticles are widely used as a highly generalizable tool to entrap a range of different drugs for controlled or site-specific release. However, despite numerous studies examining the kinetics of controlled release, the biological behavior of such nanoparticles remains poorly understood, particularly with respect to endocytosis and intracellular trafficking. We synthesized polyethylenimine-decorated polymer nanospheres (ca. 100-250 nm) of the type commonly used for drug release and used correlated electron microscopy, fluorescence spectroscopy and microscopy, and relaxometry to track endocytosis in neural cells. These capabilities provide insight into how polyethylenimine mediates the entry of nanoparticles into neural cells and show that polymer nanosphere uptake involves three distinct steps, namely, plasma membrane attachment, fluid-phase as well as clathrin- and caveolin-independent endocytosis, and progressive accumulation in membrane-bound intracellular vesicles. These findings provide detailed insight into how the intracellular delivery of nanoparticles is mediated by polyethylenimine, which is presently the most commonly used nonviral gene transfer agent. This fundamental knowledge may also assist in the preparation of next-generation nonviral vectors.

Manipulating cellular interactions of poly(glycidyl methacrylate) nanoparticles using mixed polymer brushes

Publisher: American Chemical Society (ACS)

Date: 22-09-2016

DOI: 10.1021/ACSMACROLETT.6B00613

Abstract: There is a growing need for the development of nanoparticles, with imaging and drug delivery capabilities, to maintain cellular uptake but avoid protein attachment and recognition. In this study we have demonstrated that nanoparticles consisting of a poly(glycidyl methacrylate) (PGMA) core and a mixed brush architecture of methoxypoly(ethylene glycol) and poly(ethylenimine) (mPEG-PEI) on the surface can meet this need. Surface functionalization with PEI alone results in cellular uptake, but rapid protein attachment whereas PEG alone can avoid protein attachment but to the detriment of cellular uptake. A mixed copolymer brush of both PEI and mPEG provides the ideal balance.

Schwann Cells Overexpressing FGF-2 Alone or Combined with Manual Stimulation Do Not Promote Functional Recovery after Facial Nerve Injury

Publisher: Hindawi Limited

Date: 2009

DOI: 10.1155/2009/408794

Abstract: Purpose . To determine whether transplantation of Schwann cells (SCs) overexpressing different isoforms of fibroblast growth factor 2 (FGF-2) combined with manual stimulation (MS) of vibrissal muscles improves recovery after facial nerve transection in adult rat. Procedures . Transected facial nerves were entubulated with collagen alone or collagen plus naïve SCs or transfected SCs. Half of the rats received daily MS. Collateral branching was quantified from motoneuron counts after retrograde labeling from 3 facial nerve branches. Quality assessment of endplate reinnervation was combined with video-based vibrissal function analysis. Results . There was no difference in the extent of collateral axonal branching. The proportion of polyinnervated motor endplates for either naïve SCs or FGF-2 over-expressing SCs was identical. Postoperative MS also failed to improve recovery. Conclusions . Neither FGF-2 isoform changed the extent of collateral branching or polyinnervation of motor endplates furthermore, this motoneuron response could not be overridden by MS.

Failure to restore vision after optic nerve regeneration in reptiles : interspecies variation in response to axotomy

Publisher: Wiley

Date: 14-09-2004

DOI: 10.1002/CNE.20299

Abstract: Optic nerve regeneration within the reptiles is variable. In a snake, Viper aspis, and the lizard Gallotia galloti, regeneration is slow, although some retinal ganglion cell (RGC) axons eventually reach the visual centers (Rio et al. [1989] Brain Res 479:151-156 Lang et al. [1998] Glia 23:61-74). By contrast, in a lizard, Ctenophorus ornatus, numerous RGC axons regenerate rapidly to the visual centers, but unless animals are stimulated visually, the regenerated projection lacks topography and animals remain blind via the experimental eye (Beazley et al. [2003] J. Neurotrauma 20:1263-1269). V. aspis, G. galloti, and C. ornatus belong respectively to the Serpentes, Lacertidae, and Agamidae within the Eureptilia, the major modern group of living reptiles comprising the Squamata (snakes, lizards, and geckos) and the Crocodyllia. Here we have extended the findings on Eureptilia to include two geckos (Gekkonidae), Cehyra variegata and Nephrurus stellatus. We also examined a turtle, Chelodina oblonga, the Testudines being the sole surviving representatives of the Parareptilia, the more ancient reptilian group. In all three species, visually elicited behavioral responses were absent throughout regeneration, a result supported electrophysiologically axonal tracing revealed that only a small proportion of RGC axons crossed the lesion and none entered the contralateral optic tract. RGC axons failed to reach the chiasm in C. oblonga, and in G. variegata, and N. stellatus RGC axons entered the opposite optic nerve a limited ipsilateral projection was seen in G. variegata. Our results support a heterogeneous response to axotomy within the reptiles, each of which is nevertheless dysfunctional.

Manual stimulation of the orbicularis oculi muscle improves eyelid closure after facial nerve injury in adult rats

Publisher: Wiley

Date: 02-2009

DOI: 10.1002/MUS.21126

Abstract: We have shown that manual stimulation of rat whisker-pad muscles following facial-facial-anastomosis (FFA) restores normal whisking by lowering the proportion of polyinnervated motor endplates. Here we examined whether manual stimulation of the orbicularis oculi muscle (OOM) after FFA would also improve outcome. Blink responses to standardized air puffs were analyzed using video-based motion analysis. Two months after FFA, blink capacity was impaired, as indicated by a largely increased minimum distance between the eyelids after air-puff stimulation compared with intact rats (2.7 +/- 0.4 vs. 0.2 +/- 0.01 mm). Manual stimulation reduced this deficit by a factor of two (1.3 +/- 0.5 mm). The functional improvement after manual stimulation was associated with a 2-fold decrease in the proportion of polyinnervated OOM endplates (21 +/- 10% vs. 42 +/- 10% without manual stimulation, 0% in intact rats). We conclude that manual stimulation is a noninvasive and simple procedure with immediate potential for clinical rehabilitation of eyelid closure following facial nerve injury.

Manual Stimulation of the Suprahyoid-Sublingual Region Diminishes Polynnervation of the Motor Endplates and Improves Recovery of Function After Hypoglossal Nerve Injury in Rats

Publisher: SAGE Publications

Date: 08-07-2008

DOI: 10.1177/1545968308316387

Abstract: Background. Using the rat facial nerve axotomy model, the authors recently showed that manual stimulation of denervated whiskerpad muscles reduced the posttransectional polyinnervation at the neuromuscular junctions and promoted full recovery of vibrissal whisking. Objective. Prompted by implications for rehabilitation therapy, the authors examined whether manual stimulation of denervated supra- and infrahyoid muscles would also improve recovery after unilateral lesion on the hypoglossal nerve. Methods. Adult rats underwent transection of the right hypoglossal nerve. Half of the animals received no postoperative treatment, and the other half were subjected to daily manual stimulation of the suprahyoid/sublingual region for 2 months. Recovery was assessed by measuring the angle of tongue-tip deviation from the midline, degree of collateral axonal branching at the lesion site (counts after retrograde labeling with 2 fluorescent dyes), synaptic input to the hypoglossal motoneurons using synaptophysin immunocytochemistry, tongue-muscles motor representation in the cerebral cortex after c-Fos immunocytochemistry, and portion of polyinnervated neuromuscular junctions. Results. In animals receiving manual stimulation, the tongue-tip deviation was 37.0 ± 49.37°, whereas values in control nonstimulated rats were significantly higher (50.1 ± 9.01° P .05 mean ± SD). Improved recovery was not associated with reduced collateral axonal branching there were also no differences in tongue-muscles representation in the motor cortex. However, manual stimulation restored the total synaptic input to levels in intact animals and reduced the proportion of polyinnervated neuromuscular junctions compared with nonstimulated animals. Conclusion. The data show that manual stimulation of denervated muscles improves functional outcome following peripheral nerve injury. This suggests immediate potential for enhancing clinical rehabilitation strategies.

Regional and cellular distribution of ephrin-B1 in adult mouse brain

Publisher: Elsevier BV

Date: 2009

DOI: 10.1016/J.BRAINRES.2008.09.100

Abstract: The membrane-bound proteins ephrins and their receptors, Eph receptor tyrosine kinases, are known for their key role during development of the central nervous system (CNS). Ligand/receptor interactions as a result of cell-cell contacts activate intracellular signalling pathways which mediate specific cellular responses. Activation can occur bidirectionally in both the receptor and the ligand-bearing cells. Eph receptor and ephrin families have been implicated in synaptic plasticity in the mature brain: effects include long-term potentiation/depression of excitatory transmission (LTP/LTD) and an action on the structure and number of synaptic contacts. However, due to the redundancy of binding between receptors and ligands, the role of in idual proteins has not yet been completely elucidated. Ephrin-B1 has been suggested to play a role in synaptic plasticity in the hippoc us, but its expression and localization at pre- or post-synaptic sites has been poorly documented, most likely due to the apparent low activity of the corresponding gene in mature brain. Here we present immunohistochemical data demonstrating a broad but highly regulated cellular distribution of ephrin-B1 in the mature mouse brain. We show that ephrin-B1 is expressed post-synaptically on dendritic spines in the cortex, supporting a role in synaptic plasticity in this region. However, the prevalent extra-synaptic distribution in regions such as the hippoc us and cerebellum suggests an additional structural role, perhaps at the neuron/glia interface.

The effects of concentration-dependent morphology of self-assembling RADA16 nanoscaffolds on mixed retinal cultures

Publisher: Royal Society of Chemistry (RSC)

Date: 2011

DOI: 10.1039/C0NR00666A

Abstract: RADA16 self-assembling peptide nanofiber scaffolds (SAPNSs) have been shown to have positive effects on neural regeneration following injury to the central nervous system in vivo, but mechanisms are unclear. Here we show that RADA16 SAPNSs form scaffolds of increasing fiber density with increasing peptide concentration which in turn has a concentration-dependent effect on neurons and astrocytes in mixed retinal cultures. Importantly, we report that the final nanoscale fiber architecture is an important factor to consider in designing scaffolds to promote regeneration in the central nervous system.

Developing a spinal cord injury research strategy using a structured process of evidence review and stakeholder dialogue. Part II: Background to a research strategy.

Publisher: Springer Science and Business Media LLC

Date: 23-06-2015

DOI: 10.1038/SC.2015.86

Abstract: Literature review/semi-structured interviews. To develop a spinal cord injury (SCI) research strategy for Australia and New Zealand. Australia. The National Trauma Research Institute Forum approach of structured evidence review and stakeholder consultation was employed. This involved gathering from published literature and stakeholder consultation the information necessary to properly consider the challenge, and synthesising this into a briefing document. A research strategy 'roadmap' was developed to define the major steps and key planning questions to consider next, evidence from published SCI research strategy initiatives was synthesised with information from four one-on-one semi-structured interviews with key SCI research stakeholders to create a research strategy framework, articulating six key themes and associated activities for consideration. These resources, combined with a review of SCI prioritisation literature, were used to generate a list of draft principles for discussion in a structured stakeholder dialogue meeting. The research strategy roadmap and framework informed discussion at a structured stakeholder dialogue meeting of 23 participants representing key SCI research constituencies, results of which are published in a companion paper. These resources could also be of value in other research strategy or planning exercises. This project was funded by the Victorian Transport Accident Commission and the Australian and New Zealand Spinal Cord Injury Network.

Intravesical hyaluronic acid with chondroitin sulphate to prevent urinary tract infection after spinal cord injury

Publisher: Informa UK Limited

Date: 06-07-2022

DOI: 10.1080/10790268.2022.2089816

Abstract: Prevention of urinary tract infection (UTI) after spinal cord injury is an important goal. Intravesical hyaluronic acid with chondroitin sulphate (HA+CS) has been effective in preventing UTI in other settings. We aimed to demonstrate safety and feasibility of a standard treatment course of 7 intravesical HA+CS instillations over 12 weeks, in patients with acute (Arm A) and chronic (Arm B) spinal cord injury (SCI). Follow-up of adverse events, quality of life bladder management difficulty (BMD) and bladder complication (BC) Of 33 and 14 in iduals screened, 2 and 8 participants were recruited to the study for Arm A and Arm B respectively. Of the 10 participants, 8 completed all 7 instillations. HA+CS commonly caused cloudy urine with urinary sediment which was mild and short-lived. In Arm B, a mean reduction in BMD and BC T-scores was observed from baseline (57.3 and 54.4 respectively), of 6.8 and 4.3 at 12 weeks and 1.6 and 2.8 at 24 weeks, respectively. Four participants with a history of frequent UTI in the prior 12 months did not have UTI in the 24 weeks of the study. HA+CS was well tolerated. Recruitment was more difficult in early acute SCI participants with chronic SCI were highly motivated to reduce UTI and manage self-administration without difficulty. Larger case-control or randomized controlled trials in patients with neurogenic bladder from SCI are warranted. ClinicalTrials.gov identifier: NCT03945110.

Developing a spinal cord injury research strategy using a structured process of evidence review and stakeholder dialogue. Part III: outcomes

Publisher: Springer Science and Business Media LLC

Date: 23-06-2015

DOI: 10.1038/SC.2015.87

Abstract: Focus Group. To develop a unified, regional spinal cord injury (SCI) research strategy for Australia and New Zealand. Australia. A 1-day structured stakeholder dialogue was convened in 2013 in Melbourne, Australia, by the National Trauma Research Institute in collaboration with the SCI Network of Australia and New Zealand. Twenty-three experts participated, representing local and international research, clinical, consumer, advocacy, government policy and funding perspectives. Preparatory work synthesised evidence and articulated draft principles and options as a starting point for discussion. A regional SCI research strategy was proposed, whose objectives can be summarised under four themes. (1) Collaborative networks and strategic partnerships to increase efficiency, reduce duplication, build capacity and optimise research funding. (2) Research priority setting and coordination to manage competing studies. (3) Mechanisms for greater consumer engagement in research. (4) Resources and infrastructure to further develop SCI data registries, evaluate research translation and assess alignment of research strategy with stakeholder interests. These are consistent with contemporary international SCI research strategy development activities. This first step in a regional SCI research strategy has articulated objectives for further development by the wider SCI research community. The initiative has also reinforced the importance of coordinated, collective action in optimising outcomes following SCI.

An in vitro technique for electrophysiological mapping of reptilian retinotectal projections

Publisher: Elsevier BV

Date: 06-1998

DOI: 10.1016/S0165-0270(98)00020-X

Abstract: An in vitro procedure is described for electrophysiological mapping of the retinotectal projections using an eye-cup and brain stem preparation which remains viable for up to 30 h. The technique has been found to be successful in turtles and lizards and may be useful for other species in which metabolism is greatly depressed by low temperatures. There are several advantages over in vivo recording, including the longevity and stability of the preparation, an absence of confounding anaesthetic effects and the ability to record from the retina as well as from the brain. The technique offers opportunities to introduce pharmacological agents via the perfusate or to conduct anatomical tracing studies coincident with electrophysiological recording.

Characterization of polymeric nanoparticles for treatment of partial injury to the central nervous system

Publisher: Elsevier BV

Date: 06-2016

DOI: 10.1016/J.DIB.2016.02.019

The balance of NMDA- and AMPA/kainate receptor-mediated activity in normal adult goldfish and during optic nerve regeneration

Publisher: Elsevier BV

Date: 10-2005

DOI: 10.1016/J.EXPNEUROL.2005.05.015

Abstract: Retinotectal topography is established during development and relies on the sequential recruitment of glutamate receptors within postsynaptic tectal cells. NMDA receptors underpin plastic changes at early stages when retinal ganglion cell (RGC) terminal arbors are widespread and topography is coarse AMPA/kainate receptors mediate fast secure neurotransmission characteristic of mature circuits once topography is refined. Here, we have examined the relative contributions of these receptors to visually evoked activity in normal adult goldfish, in which retinotectal topography is constantly adjusted to compensate for the continual neurogenesis and the addition of new RGC arbors. Furthermore, we examined animals at two stages of optic nerve regeneration. In the first, RGC arbors are widespread and receptive fields large resulting in coarse topography in the second, RGC arbors are pruned to reduce receptive fields leading to refined topography. Antagonists were applied to the tectum during multiunit recording of postsynaptic responses. Normal goldfish have low levels of NMDA receptor-mediated activity and high levels of AMPA/kainate. When coarse topography has been restored, NMDA receptor-mediated activity is increased and that of AMPA/kainate decreased. Once topography has been refined, the balance of NMDA and AMPA/kainate receptor-mediated activity returns to normal. The data suggest that glutamatergic neurotransmission in normal adult goldfish is dual with NMDA receptors fine-tuning topography and AMPA receptors allowing stable synaptic function. Furthermore, the normal operation of both receptors allows a response to injury in which the balance can be transiently reversed to restore topography and vision.

Poor functional recovery and muscle polyinnervation after facial nerve injury in fibroblast growth factor-2-/- mice can be improved by manual stimulation of denervated vibrissal muscles

Publisher: Elsevier BV

Date: 05-2011

DOI: 10.1016/J.NEUROSCIENCE.2011.03.032

Abstract: Functional recovery following facial nerve injury is poor. Adjacent neuromuscular junctions (NMJs) are "bridged" by terminal Schwann cells and numerous regenerating axonal sprouts. We have recently shown that manual stimulation (MS) restores whisking function and reduces polyinnervation of NMJs. Furthermore, MS requires both insulin-like growth factor-1 (IGF-1) and brain-derived neurotrophic factor (BDNF). Here, we investigated whether fibroblast growth factor-2 (FGF-2) was also required for the beneficial effects of MS. Following transection and suture of the facial nerve (facial-facial anastomisis, FFA) in homozygous mice lacking FGF-2 (FGF-2(-/-)), vibrissal motor performance and the percentage of poly-innervated NMJ were quantified. In intact FGF-2(-/-) mice and their wildtype (WT) counterparts, there were no differences in litude of vibrissal whisking (about 50°) or in the percentage of polyinnervated NMJ (0%). After 2 months FFA and handling alone (i.e. no MS), the litude of vibrissal whisking in WT-mice decreased to 22±3°. In the FGF-2(-/-) mice, the litude was reduced further to 15±4°, that is, function was significantly poorer. Functional deficits were mirrored by increased polyinnervation of NMJ in WT mice (40.33±2.16%) with polyinnervation being increased further in FGF-2(-/-) mice (50.33±4.33%). However, regardless of the genotype, MS increased vibrissal whisking litude (WT: 33.9°±7.7 FGF-2(-/-): 33.4°±8.1) and concomitantly reduced polyinnervation (WT: 33.9%±7.7 FGF-2(-/-): 33.4%±8.1) to a similar extent. We conclude that, whereas lack of FGF-2 leads to poor functional recovery and target reinnervation, MS can nevertheless confer some functional benefit in its absence.

A biphasic sequence and myelination in the optic nerve of the frog

Publisher: Wiley

Date: 07-1993

DOI: 10.1002/CNE.903330107

Abstract: We have examined the sequence of myelination along the optic nerve of the frog Litoria (Hyla) moorei from early tadpole life to adulthood. Myelinated axons were counted in electron micrographs of transverse sections taken from behind the eye, at the optic foramen and the chiasm. In tadpoles, myelinated axon numbers were significantly higher at the foramen than at the other levels. By metamorphic climax, numbers had risen at all three levels but more so behind the eye and at the chiasm to become approximately equal along the nerve. After metamorphosis, there was a dramatic increase in myelinated axon numbers, but another pattern was seen in frogs of 5 cm and 7 cm body length, counts were significantly higher at the chiasm than at the foramen and lowest behind the eye. Thereafter, myelinated axon numbers stabilized at the chiasm but increased behind the eye and at the foramen so that in the most mature stage for this species, 9 cm adults, counts were again similar at the three levels. In addition, total axon numbers, that is, myelinated plus unmyelinated, were assessed from electron micrographs and increased from approximately 8,500 in early tadpoles to 0.65 million in fully mature adults. The proportion of axons that were myelinated showed two peaks, one before and the other after metamorphosis. Measurements of axon diameters from electron micrographs suggested that there was a critical diameter for myelination of 0.3 microns before, and of 0.5 microns after metamorphosis. The data indicate that there is a biphasic sequence of myelination of optic axons, the first phase being pre-metamorphic and the second post-metamorphic. The first phase is initiated at the foramen, and then extends both towards the eye and chiasm and continues until metamorphic climax. During the second phase, myelination originates at the chiasm, spreads towards the eye, and is complete only in the most mature adults. The critical diameter for myelination is smaller in the first phase than in the second.

Axonal Sprouting in the Optic Nerve Is Not a Prerequisite for Successful Regeneration

Publisher: Wiley

Date: 03-09-2003

DOI: 10.1002/CNE.10782

Abstract: Axonal sprouting, the production of axons additional to the parent one, occurs during optic nerve regeneration in goldfish and the frog Rana pipiens, with numbers of regenerate axons exceeding normal values four- to sixfold (Murray [1982] J. Comp. Neurol. 209:352-362 Stelzner and Strauss [1986] J. Comp. Neurol. 245:83-103). To determine whether axonal sprouting is a prerequisite for regeneration, the frog Litoria moorei was examined, a species that undergoes successful optic nerve regeneration but with a different time course compared with R. pipiens. Sprouting was assessed, as in goldfish and R. pipiens, from electron microscopic counts between the lesion and chiasm. However, disconnected axons that persist after axotomy would have falsely elevated the counts. The suspected overlap of these two axon populations was confirmed by labeling regenerate axons anterogradely with DiI (1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate) and disconnected ones retrogradely with DiA (4-4-dihexadecylaminostyrl 1-N methylpyridinium iodide). Numbers of disconnected axons were estimated after preventing regeneration and subtracted from numbers in regenerate nerves. Throughout, the total number of regenerate axons was approximately one third lower than normal (P < 0.05) supporting a previous finding of minimal axonal sprouting in L. moorei (Dunlop et al. [2002] J. Comp. Neurol. 446:276-287). The validity of the subtractive electron microscopic method was confirmed by retrograde labeling to estimate numbers of retinal ganglion cells whose axons had crossed the lesion values were approximately one third lower than normal. The data suggest that sprouting is not essential for either axon outgrowth or topographic map refinement.

Development of primary visual projections occurs entirely postnatally in the fat-tailed dunnart, a marsupial mouse, Sminthopsis crassicaudata

Publisher: Wiley

Date: 21-07-1997

DOI: 10.1002/(SICI)1096-9861(19970721)384:1<26::AID-CNE2>3.0.CO;2-N

Abstract: The quaternary organization of rhodopsin-like G protein-coupled receptors in native tissues is unknown. To address this we generated mice in which the M

Wiring up the visual system

Publisher: Wiley

Date: 08-1995

DOI: 10.1111/J.1440-1681.1995.TB02065.X

Abstract: 1. In this review we describe some of our recent studies on the developing marsupial visual pathway. The description focuses on retinal ganglion cells, considering the formation of their dendritic trees, the outgrowth of axons and the formation of connections within the brain. 2. Both dendritic trees and outgrowing axons undergo a period of exuberance, followed by one of refinement. The dendritic tree transiently develops a more complex branching pattern than is found in adults. Short side branches, referred to as spines, are a feature of immature dendrites and, to a lesser extent, of axons. These structures are mostly lost as development proceeds. However, they are retained on the dendritic trees of small-field ganglion cells and, for a proportion of axons, on that part within the nerve fibre layer of the retina. Although most axons navigate fairly direct routes towards their targets, a minority follow inappropriate courses, such as doubling back towards the eye or entering the opposite optic nerve at the chiasm. As such errant axons are not seen in the adult, we assume that their parent cell bodies die during development. 3. Throughout development, optic axons are arranged in an approximate retinotopic order along the length of the visual pathway as a result, axons approach the visual centres aligned to form, at least, a crude retinotopic map. Axons from dorsal and ventral retina exchange locations along the optic nerve and in this way correct for the inversion of the image brought about by the lens.(ABSTRACT TRUNCATED AT 250 WORDS)

Buy-now-pay-later

Publisher: Wiley

Date: 11-2021

DOI: 10.1111/JPC.15777

Abstract: More than 8 billion tonnes of plastic were produced between 1950 and 2015, that is 1 tonne for every man, woman and child on our planet. Global plastic production has been growing exponentially with an annual growth rate of 8.4% since 1950, equating to approximately 380 million tonnes per annum. A further 50 kg of plastic is now being produced for each person every year with production continuing to accelerate. Here, we discuss the human and planetary health hazards of all that plastic. We consider each step in the journey of these complex and pervasive industrial materials: from their synthesis predominantly from fossil fuel feedstocks, through an often‐brief consumer use as plastic products, and onto waste streams as fuel, permanent landfill or as unmanaged waste in our environment, food, air and bodies.

Topographic order of retinofugal axons in a marsupial: implications for map formation in visual nuclei

Publisher: Wiley

Date: 2000

DOI: 10.1002/1096-9861(20001204)428:1<33::AID-CNE4>3.0.CO;2-K

Exogenous metallothionein‐IIA promotes accelerated healing after a burn wound

Publisher: Wiley

Date: 09-2008

DOI: 10.1111/J.1524-475X.2008.00418.X

Early and continued manual stimulation is required for long‐term recovery after facial nerve injury

Publisher: Wiley

Date: 30-03-2017

DOI: 10.1002/MUS.25613

Abstract: We previously have shown that manual stimulation (MS) of vibrissal muscles for 2 months after facial nerve injury in rats improves whisking and reduces motor end plate polyinnervation. Here, we seek to determine whether discontinuing or delaying MS after facial-facial anastomosis (FFA) leads to similar results. Rats were subjected to FFA and received MS for (1) 4 months (early and continued), (2) the first but not the last 2 months (discontinued), or (3) the last 2 months (delayed). Intact animals and those not receiving MS (no MS) were also examined. Early and continued MS restored whisking litude to 43°, a value significantly higher compared with the discontinued, delayed, and no MS groups (32°, 24°, and 10°, respectively). Motor end plate polyinnervation occurred in all experimental groups but was significantly higher in the delayed group. Early and continued MS results in better recovery than when it is either discontinued or delayed. Muscle Nerve 57: 100-106, 2018.

Manual stimulation of forearm muscles does not improve recovery of motor function after injury to a mixed peripheral nerve

Publisher: Springer Science and Business Media LLC

Date: 23-10-2007

DOI: 10.1007/S00221-007-1174-Y

Abstract: Transection and re-anastomosis of the purely motor facial nerve leads to poor functional recovery. However, we have recently shown in rat that manual stimulation (MS) of denervated vibrissal muscles reduces the number of polyinnervated motor endplates and promotes full recovery of whisking. Here, we examined whether MS of denervated rat forearm muscles would also improve recovery following transection and suture of the mixed (sensory and motor) median nerve (median-median anastomosis, MMA). Following MMA of the right median nerve, animals received no postoperative treatment, daily MS of the forearm muscles or handling only. An almost identical level of functional recovery, measured by the force of grip in grams, was reached in all animals by the sixth postoperative week and maintained till 3 months following surgery regardless of the postoperative treatment. Also, we found no differences among the groups in the degree of axonal sprouting, the extent of motor endplate polyinnervation and in the soma size of regenerated motoneurons. Taken together, we show that while MS is beneficial following motor nerve injury, combined strategies will be required for functional recovery following mixed nerve injury.

Training on a visual task improves the outcome of optic nerve regeneration

Publisher: Mary Ann Liebert Inc

Date: 11-2003

DOI: 10.1089/089771503770802925

Abstract: Optic nerve regeneration in a lizard, Ctenophorus ornatus, is dysfunctional despite survival of most retinal ganglion cells and axon regeneration to the optic tectum. The regenerated retino-tectal projection at 6 months has crude topography but by 1 year is disordered visually-elicited behavior is absent via the experimental eye. Here, we assess the influence of training on the outcome of optic nerve regeneration. Lizards were trained to catch prey presented within the monocular field of either eye. One optic nerve was then severed and visual stimulation resumed throughout regeneration. In the trained group, presentation was restricted to the eye undergoing optic nerve regeneration for the untrained group, the unoperated eye was stimulated. Pupil responses returned in trained but not in untrained animals. At 1 year, trained animals oriented to and captured prey untrained animals demonstrated minimal orienting and failed to capture prey. Regenerated retino-tectal projections were topographic in the trained but not in the untrained group as assessed by in vitro electrophysiological recording and by carbocyanine dye tracing. In vitro electrophysiological recording during application of neurotransmitter antagonists to the tectum revealed that the level of GABAergic inhibition was modest in trained animals but elevated in the untrained group responses were mainly AMPA-mediated in both groups. We conclude that training improves the behavioral outcome of regeneration, presumably by stabilizing and refining the transient retino-tectal map and preventing a build-up of tectal inhibition. The results suggest that for successful central nerve regeneration to occur in mammals, it may be necessary to introduce training to complement procedures stimulating axon regeneration.

Minor pathological changes are induced by naltrexone-poly (DL-lactide) implants in pregnant rats

Publisher: Wiley

Date: 18-12-2009

DOI: 10.1002/JBM.A.32283

Abstract: Oral naltrexone is used to treat alcohol and heroin dependence but is associated with poor patient compliance. Sustained-release preparations have been developed to overcome noncompliance. Many sustained-release preparations are composed of polymers combined with naltrexone. Limited data indicate that polymers induce variable levels of tissue reactivity and that naltrexone may increase this effect. A slow-release subcutaneous naltrexone-poly (DL-lactide) implant is currently being trialed to treat heroin dependence in Western Australia. A minority of women fall pregnant and, although tissue reactivity in nonpregnant humans is relatively minor, detailed chronological data during pregnancy are lacking. Histological changes in pregnant rats were assessed a single active tablet containing poly[trans-3,6-dimethyl-1,4-dioxyane-2,5-dione] (DL-lactide) loaded with 25 mg of naltrexone was implanted subcutaneously, and tissue response was compared with inactive polymer implantation. Rats were timed mated at 13-26 days postimplant. Tissue assessment up to 75 days by a pathologist showed that naltrexone induced chronic inflammatory response in a dose-dependent manner, although still at a low level. Furthermore, for inactive implants, minimal foreign body reaction and fibrosis, together with low-level inflammation, suggested good long-term biocompatibility. We conclude that the Australian naltrexone-poly(DL-lactide) implant is tolerated in pregnant rats, reinforcing its potential role for managing alcohol and heroin dependence in pregnant humans.

Minimum Information about a Spinal Cord Injury Experiment: A Proposed Reporting Standard for Spinal Cord Injury Experiments

Publisher: Mary Ann Liebert Inc

Date: 08-2014

DOI: 10.1089/NEU.2014.3400

Evidence that regenerating optic axons maintain long-term growth in the Lizard Ctenophorus ornatus: Growth-associated protein-43 and gefiltin expression

Publisher: Elsevier BV

Date: 02-2001

DOI: 10.1016/S0306-4522(00)00506-6

Abstract: In the lizard, Ctenophorus ornatus, the optic nerve regenerates but animals remain blind via the experimental eye, presumably as a result of axons failing to consolidate a retinotopic map in the optic tectum. Here we have examined immunohistochemically the expression of the growth-associated protein GAP-43 and the low-molecular-weight intermediate filament protein gefiltin, up to one year after optic nerve crush. Both proteins were found to be permanently up-regulated, suggesting that regenerating axons are held in a permanent state of re-growth. We speculate that, in the lizard, the continued expression of GAP-43 and the failure to switch from the expression of low- to high-molecular-weight intermediate filament proteins are associated with the inability to consolidate a retinotopic projection.

The development and mature organisation of the end-artery retinal vasculature in a marsupial, the dunnart Sminthopsis crassicaudata

Publisher: Elsevier BV

Date: 2001

DOI: 10.1016/S0042-6989(00)00246-7

Abstract: The end-artery retinal vasculature of a marsupial, the fat-tailed dunnart, was defined by India ink injection and studied in wholemounts. In the adult, the vitreal vasculature supplying the ganglion-cell layer has major paired-vessels in a horizontal H shape. These vessels skirt the area centralis and visual streak that are supplied by fine end-loops. A second vascular layer of uniformly distributed endloops arises from the superficial vessels and lies at the inner nuclear/outer plexiform border. During development, vessels enter the eye via the optic nerve head to form the upper vasculature, assuming an essentially mature arrangement prior to the formation of the area centralis and visual streak. Vessels then descend to form the lower bed. Unlike the cat, the dunnart has retinal vessels that are patent throughout development, their growth is interstitial and reductive remodelling is not seen. A retinal end-artery system may have evolved in marsupials because their precocity requires a vasculature that is functional from early stages of development.

The AusSpinal: a test of hand function for people with tetraplegia

Publisher: Springer Science and Business Media LLC

Date: 03-08-2011

DOI: 10.1038/SC.2010.86

Abstract: Five-phased reliability and validity study. To develop and test an assessment tool designed to quantify unilateral hand function in people with tetraplegia. Seven spinal injury units in Australia. The AuSpinal is a new assessment tool comprising seven tasks designed to quantify unilateral hand function in people with tetraplegia. There were five phases in this study: (1) development of the AuSpinal (2) testing the test-retest and intrarater reliability of repeat ratings of 84 videos as determined by 13 therapists (3) testing the interrater reliability and internal consistency of simultaneous real-life ratings of eight hands as determined by six therapists (4) testing the range of scores from cross-sectional data obtained from 50 hands and (5) quantifying sensitivity to change from longitudinal data collected over the course of rehabilitation from 16 hands. The test-retest, intrarater and interrater reliabilities were high (intraclass correlation coefficients ranged from 0.79 to 0.98, 95% CI ranged from 0.72 to 1.0) with a Cronbach α-value of 0.93. There was a reasonable range in the scores obtained from the cross-sectional data of the 50 hands (interquartile range extended from 6 to 14). There was an obvious and marked change in AuSpinal scores over the course of patients' rehabilitation in 8 of the 16 hands. The AuSpinal provides a quick and reliable instrument to test hand function in people with tetraplegia. It is useful for people with poor hand function but requires the addition of more complex tasks for those with good hand function.

Recovery of whisking function promoted by manual stimulation of the vibrissal muscles after facial nerve injury requires insulin-like growth factor 1 (IGF-1)

Publisher: Elsevier BV

Date: 04-2010

DOI: 10.1016/J.EXPNEUROL.2009.12.031

Abstract: Recently, we showed that manual stimulation (MS) of denervated vibrissal muscles enhanced functional recovery following facial nerve cut and suture (FFA) by reducing poly-innervation at the neuro-muscular junctions (NMJ). Although the cellular correlates of poly-innervation are established, with terminal Schwann cells (TSC) processes attracting axon sprouts to "bridge" adjacent NMJ, molecular correlates are poorly understood. Since quantitative RT-PCR revealed a rapid increase of IGF-1 mRNA in denervated muscles, we examined the effect of daily MS for 2 months after FFA in IGF-1(+/-) heterozygous mice controls were wild-type (WT) littermates including intact animals. We quantified vibrissal motor performance and the percentage of NMJ bridged by S100-positive TSC. There were no differences between intact WT and IGF-1(+/-) mice for vibrissal whisking litude (48 degrees and 49 degrees ) or the percentage of bridged NMJ (0%). After FFA and handling alone (i.e. no MS) in WT animals, vibrissal whisking litude was reduced (60% lower than intact) and the percentage of bridged NMJ increased (42% more than intact). MS improved both the litude of vibrissal whisking (not significantly different from intact) and the percentage of bridged NMJ (12% more than intact). After FFA and handling in IGF-1(+/-) mice, the pattern was similar (whisking litude 57% lower than intact proportion of bridged NMJ 42% more than intact). However, MS did not improve outcome (whisking litude 47% lower than intact proportion of bridged NMJ 40% more than intact). We conclude that IGF-I is required to mediate the effects of MS on target muscle reinnervation and recovery of whisking function.

Effects of exogenous corticosteroids on the developing central nervous system: A review

Publisher: Ovid Technologies (Wolters Kluwer Health)

Date: 05-1999

DOI: 10.1097/00006254-199905000-00024

Abstract: Corticosteroid therapy is used in a variety of developmental clinical settings. Prenatally, maternal administration of corticosteroids is used primarily in the prevention of respiratory distress syndrome. Postnatally, corticosteroids are used to treat a variety of infant diseases such as autoimmune hemolytic anemia and hypoglycemia. Treatment regimes often involve repeated administration, on a weekly basis prenatally and daily postnatally, despite an absence of safety data from randomized clinical trials. A large number of animal studies, the majority of which used rodents, have shown that both repeated prenatal or neonatal administration of exogenous corticosteroids has a wide range of detrimental effects on the structure and function of the developing central nervous system (CNS). None of these studies included long-term follow-up. Despite the reported detrimental effects on CNS development, a number of animal studies have shown that pretreatment with corticosteroids nevertheless protect the brain from hypoxia-ischemic injury however, clinically such treatment is no longer favored. Studies using large animal models and with long-term follow-up should be undertaken to establish the relative risks and benefits of the repeated application of exogenous corticosteroids.

Protein corona formation moderates the release kinetics of ion channel antagonists from transferrin-functionalized polymeric nanoparticles

Publisher: Royal Society of Chemistry (RSC)

Date: 2020

DOI: 10.1039/C9RA09523C

Abstract: Transferrin (Tf)-functionalized p(HEMA- ran -GMA) nanoparticles were designed to incorporate and release a water-soluble combination of three ion channel antagonists, identified as a promising therapy for secondary degeneration following neurotrauma.

Effects of Immunosuppression on Regrowth of Adult Rat Retinal Ganglion Cell Axons Into Peripheral Nerve Allografts

Publisher: Wiley

Date: 21-10-2003

DOI: 10.1002/JNR.10788

Abstract: Analysis of the effectiveness of allografts and immunosuppression in the repair of nerve defects in the adult peripheral nervous system (PNS) has a long experimental and clinical history. There is little information, however, on the use of allografts in peripheral nerve (PN) transplantation into the injured central nervous system (CNS). We assessed the ability of PN allografts (from Dark-Agouti rats) to support regeneration of adult rat retinal ganglion cell (RGC) axons in immunosuppressed host Lewis rats. PN allografts were sutured onto intraorbitally transected optic nerves. Three weeks after grafting, regenerating RGC axon numbers were determined using retrograde fluorescent labelling, and total axons within PN grafts were assessed using pan-neurofilament immunohistochemistry. In the absence of immunosuppression, PN allografts contained few axons and there were very few labelled RGC. These degenerate grafts contained many T cells and macrophages. Systemic (intraperitoneal) application of the immunosuppressants cyclosporin-A or FK506 reduced cellular infiltration into allografts and resulted in extensive axonal regrowth from surviving RGCs. The average number of RGCs regenerating axons into immunosuppressed allografts was not significantly different from that seen in PN autografts in rats sham-injected with saline. Many pan-neurofilament-positive axons, a proportion of which were myelinated, were seen in immunosuppressed allografts, particularly in proximal regions of the grafts toward the optic nerve-PN interface. This study demonstrates that PN allografts can support axonal regrowth in immunosuppressed adult hosts, and points to possible clinical use in CNS repair.

Repeated prenatal corticosteroid administration delays myelination of the corpus callosum in fetal sheep

Publisher: Wiley

Date: 22-05-2001

DOI: 10.1016/S0736-5748(01)00026-0

Abstract: Glucocorticoids regulate oligodendrocyte maturation and the myelin biosynthetic pathways. Synthetic glucocorticoids, the corticosteroids have been successfully used in clinical practice as a single course to enhance lung maturation and reduce mortality and morbidity in preterm infants with no long-term neurologic or cognitive side effects. However, a trend has arisen to use repeated courses despite an absence of safety data from clinical trials. We examined the effects of clinically appropriate, maternally administrated, repeated courses of corticosteroids on myelination of the corpus callosum using sheep as a large animal model. The corpus callosum is a major white matter tract that undergoes protracted myelination, underpins higher order cognitive processing and developmental damage to which is associated with, for ex le, cerebral palsy, mental retardation and attention deficit hyperactivity disorder. Pregnant ewes were given saline or betamethasone (0.5 mg/kg) at 104,111,118 and 124 days gestation, stages equivalent to the third trimester in humans. Lambs were delivered at 145 days (term), perfused and the corpus callosum examined light and electron microscopically. Total axon numbers were unaffected (P>0.05). However, myelination was significantly delayed. Myelinated axons were 5.7% in the experimental group and 9.2% in controls (P<0.05) conversely, unmyelinated axons were 88.3 and 83.7% (P<0.05). Myelinated axon diameter and myelin sheath thickness were also reduced (0.68 vs. 0.94 and 0.11 vs. 0.14 microm, P<0.05). Our data suggest that repeated prenatal corticosteroid administration delays myelination of the corpus callosum and that further safety data are needed to evaluate clinical practice.

A scoping review protocol on in vivo human plastic exposure and health impacts

Publisher: Springer Science and Business Media LLC

Date: 05-07-2022

DOI: 10.1186/S13643-022-02010-6

Abstract: Global plastic production has increased exponentially since the 1960s, with more than 6300 million metric tons of plastic waste generated to date. Studies have found a range of human health outcomes associated with exposure to plastic chemicals. However, only a fraction of plastic chemicals used have been studied in vivo, and then often in animals, for acute toxicological effects. With many questions still unanswered about how long-term exposure to plastic impacts human health, there is an urgent need to map human in vivo research conducted to date, casting a broad net by searching terms for a comprehensive suite of plastic chemical exposures and the widest range of health domains. This protocol describes a scoping review that will follow the recommended framework outlined in the 2017 Guidance for the Conduct of Joanna Briggs Institute (JBI) Scoping Reviews , to be reported in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) Checklist . A literature search of primary clinical studies in English from 1960 onwards will be conducted in MEDLINE (Ovid) and EMBASE (Ovid) databases. References eligible for inclusion will be identified through a quality-controlled, multi-level screening process. Extracted data will be presented in diagrammatic and tabular form, with a narrative summary addressing the review questions. This scoping review will comprehensively map the primary research undertaken to date on plastic exposure and human health. Secondary outputs will include extensive databases on plastic chemicals and human health outcomes/impacts. Open Science Framework (OSF)-Standard Pre-Data Collection Registration, etails/osf-registrations-gbxps-v1 , 0.17605/OSF.IO/GBXPS

Synthesis and toxicology of p-phosphonic acid calixarenes and O-alkylated analogues as potential calixarene-based phospholipids

Publisher: Wiley

Date: 03-2012

DOI: 10.1002/CPLU.201100081

Antioxidant phospholipid calix[4]arene mimics as micellular delivery systems

Publisher: Royal Society of Chemistry (RSC)

Date: 2013

DOI: 10.1039/C3OB41178H

Abstract: Amphiphilic calix[4]arenes were designed as phospholipid mimics by incorporating PO3H2 or NMe3(+) head groups. Using PC12 cells and three stressors (H2O2, menadione and glutamate), we established safe calix[4]arene levels that are able not only to deliver antioxidant payloads of curcumin, but intriguingly also have inherent antioxidant properties. The calix[4]arenes appear to be potent synthetic antioxidants that could be used as nano-carriers for drug delivery.

Development of visual projections follows an avian/mammalian-like sequence in the lizard Ctenophorus ornatus

Publisher: Wiley

Date: 30-09-2002

DOI: 10.1002/CNE.10394

Abstract: Development of primary visual projections was examined in a lizard Ctenophorus ornatus by anterograde and retrograde tracing with DiI and by GAP-43 immunohistochemistry. Visual pathway development was essentially similar to that in birds and mammals and thus differed from patterns in fish or hibians. A number of features characterised the development as mammalian-like. Three phases occurred in rapid succession after laying: outgrowth (2-3 weeks, early), exuberance (4-5 weeks, intermediate), and retraction to the adult pattern (6-8 weeks, late) at about the time of hatching and eye opening. Furthermore, ipsilateral projections developed with only a slight lag relative to the contralateral ones. The dorsally located fovea could be identified from early stages. Optic axons formed transient exuberant projections to the ipsilateral optic tectum, to the opposite optic nerve, and to nonvisual regions. The pattern resembled that formed in the long term by regenerating optic axons in C. ornatus (Dunlop et al. [2000b] J. Comp. Neurol. 416:188-200), suggesting that axons recognise molecular signals associated with the initial exuberant innervation but not those associated with subsequent refinement.

Secondary degeneration of the optic nerve following partial transection : the benefits of lomerizine

Publisher: Elsevier BV

Date: 03-2009

DOI: 10.1016/J.EXPNEUROL.2008.11.026

Abstract: Secondary degeneration is a form of 'bystander' damage that can affect neural tissue both nearby and remote from an initial injury. Partial optic nerve transection is an excellent model in which to unequivocally differentiate events occurring during secondary degeneration from those resulting from primary CNS injury. We analysed the primary injury site within the optic nerve (ON) and intact areas vulnerable to secondary degeneration. Areas affected by the primary injury showed morphological disruption, loss of beta-III tubulin axonal staining, reduced myelinated axon density, greater proteoglycan expression (phosphacan), increased microglia and macrophage numbers and increased oxidative stress. Similar, but less extreme, changes were seen in areas of the optic nerve undergoing secondary degeneration. The CNS-specific L- and T-type calcium channel blocker lomerizine alleviated some of the changes in areas vulnerable to secondary degeneration. Lomerizine reduced morphological disruption, oxidative stress and phosphacan expression, and limited early increases in macrophage numbers. However, lomerizine failed to prevent progressive de-myelination of ON axons. Within the retina, secondary retinal ganglion cell (RGC) death was significant in areas vulnerable to secondary degeneration. Lomerizine protected RGCs from secondary death at 4 weeks but did not fully restore behavioural function (optokinetic nystagmus). We conclude that blockade of calcium channels is neuroprotective and limits secondary degenerative changes following CNS injury. However such an approach may need to be combined with other treatments to ensure long-term maintenance of full visual function.

Early events of Secondary Degeneration after Partial Optic Nerve Transection: An Immunohistochemical Study

Publisher: Mary Ann Liebert Inc

Date: 02-2010

DOI: 10.1089/NEU.2009.1112

Abstract: Secondary degeneration in the central nervous system involves indirect damage to neurons and glia away from the initial injury. Partial transection of the dorsal optic nerve (ON) results in precise spatial separation of the primary trauma from delayed degenerative events in ventrally placed axons and parent somata. Here we conduct an immunohistochemical survey of secondary cellular changes in and around axons and their parent retinal ganglion cell (RGC) somata during the first 3 days after a restricted, dorsal ON transection. This is before the secondary loss of RGCs and axons projecting through the uninjured, ventral portion of the ON. Within 5 min, manganese superoxide dismutase (MnSOD a marker of oxidative stress) co-localizes within the astrocytic network across the entire profile of the ON. Secondary astrocyte hypertrophy of immunofluorescent labeling was evident from 3 h, with sustained increases in myelin basic protein immunoreactivity across the nerve by 24 h. Increases in NG-2-positive oligodendrocyte precursor cells, ED-1-positive activated microglia/macrophages, and Iba1-positive reactive resident microglia/macrophage numbers were only seen in ON vulnerable to secondary degeneration by 3 days. Changes within RGC somata exclusively vulnerable to secondary degeneration were detected at 24 h, as evidenced by increases in MnSOD immunoreactivity, followed by increases in c-jun immunoreactivity at 3 days. Treatment with the voltage-gated calcium channel blocker lomerizine did not alter any measured outcome. We conclude that oxidative stress spreading via the astrocytic network and from injured axons to parent RGC somata is an early event during secondary degeneration, and containment is likely to be required in order to prevent further damage to the nerve.

The effects of maternally administered methadone, buprenorphine and naltrexone on offspring: Review of human and animal data

Publisher: Bentham Science Publishers Ltd.

Date: 06-2008

DOI: 10.2174/157015908784533842

Neural Development in Metatherian and Eutherian Mammals: Variation and Constraint

Publisher: Wiley

Date: 30-08-1999

DOI: 10.1002/(SICI)1096-9861(19990830)411:3<359::AID-CNE1>3.0.CO;2-J

Striking Denervation of Neuromuscular Junctions without Lumbar Motoneuron Loss in Geriatric Mouse Muscle

Publisher: Public Library of Science (PLoS)

Date: 02-12-2011

DOI: 10.1371/JOURNAL.PONE.0028090

Neural Activity and Facilitated Recovery by Training After CNS Injury: Implications for Rehabilitation

Publisher: American Spinal Injury Association

Date: 04-2003

DOI: 10.1310/C8CQ-KTB2-9QJX-C4GX

Use of a Y-tube-conduit Following Facial Nerve Injury Reduces Collateral Axonal Branching at the Lesion Site but Neither Reduces Polyinnervation of Motor Endplates Nor Improves Functional Recovery

Publisher: Ovid Technologies (Wolters Kluwer Health)

Date: 06-2012

DOI: 10.1227/NEU.0B013E318249F16F

Retinal Characteristics of the Ornate Dragon Lizard, Ctenophorus ornatus

Publisher: Wiley

Date: 25-07-2002

DOI: 10.1002/CNE.10308

Abstract: The retina of a diurnal insectivorous lizard, Ctenophorus ornatus (Agamidae) was investigated using microspectrophotometry and light and electron microscopy. A prominent broad yellow band was observed that extended across the mid-retina. The yellow coloration was found to originate from both oil droplets and diffuse pigmentation within cone inner segments. Microspectrophotometric analysis revealed yellow oil droplets with variable absorption of wavelengths below 520 nm and transparent oil droplets with no detectable absorptance between 350 and 750 nm. Cones with transparent oil droplets lacked the diffuse yellow pigmentation. The mean wavelengths of maximum absorbance of visual pigments in the isolated cone outer segments were at 440, 493, and 571 nm. The retina was found to possess a deep convexiclivate fovea located within the yellow band, slightly dorsotemporal of the retinal midpoint. The topography of the retinal ganglion cells revealed that the fovea was contained within an area centralis. Photoreceptors were either single (80%) or unequal double (20%) cones. Within the region of the fovea, the cones were approximately 20% the diameter of those in the peripheral retina. Colored oil droplets and yellow pigment may increase visual acuity by absorbing short wavelength light scattered either by the atmosphere or the optical structures of the eye. The presence of a fovea containing slender cone photoreceptors and three visual pigments suggests that the lizard has high acuity and the potential for color vision.

Non-invasive stimulation of the vibrissal pad improves recovery of whisking function after simultaneous lesion of the facial and infraorbital nerves in rats

Publisher: Springer Science and Business Media LLC

Date: 28-04-2011

DOI: 10.1007/S00221-011-2697-9

Abstract: We have recently shown that manual stimulation of target muscles promotes functional recovery after transection and surgical repair to pure motor nerves (facial: whisking and blink reflex hypoglossal: tongue position). However, following facial nerve repair, manual stimulation is detrimental if sensory afferent input is eliminated by, e.g., infraorbital nerve extirpation. To further understand the interplay between sensory input and motor recovery, we performed simultaneous cut-and-suture lesions on both the facial and the infraorbital nerves and examined whether stimulation of the sensory afferents from the vibrissae by a forced use would improve motor recovery. The efficacy of 3 treatment paradigms was assessed: removal of the contralateral vibrissae to ensure a maximal use of the ipsilateral ones (vibrissal stimulation Group 2), manual stimulation of the ipsilateral vibrissal muscles (Group 3), and vibrissal stimulation followed by manual stimulation (Group 4). Data were compared to controls which underwent surgery but did not receive any treatment (Group 1). Four months after surgery, all three treatments significantly improved the litude of vibrissal whisking to 30° versus 11° in the controls of Group 1. The three treatments also reduced the degree of polyneuronal innervation of target muscle fibers to 37% versus 58% in Group 1. These findings indicate that forced vibrissal use and manual stimulation, either alone or sequentially, reduce target muscle polyinnervation and improve recovery of whisking function when both the sensory and the motor components of the trigemino-facial system regenerate.

Demonstrating efficacy in preclinical studies of cellular therapies for spinal cord injury — How much is enough?

Publisher: Elsevier BV

Date: 10-2013

DOI: 10.1016/J.EXPNEUROL.2013.05.012

Abstract: Cellular therapies represent a novel treatment approach for spinal cord injury (SCI), with many different cellular substrates showing promise in preclinical animal models of SCI. Considerable interest therefore exists to translate such cellular interventions into human clinical trials. Balanced against the urgency for clinical translation is the desire to establish the robustness of a cellular therapy's efficacy in preclinical studies, thereby optimizing its chances of succeeding in human trials. Uncertainty exists, however, on the extent to which a therapy needs to demonstrate efficacy in the preclinical setting in order to justify the initiation of a lengthy, expensive, and potentially risky clinical trial. The purpose of this initiative was to seek perspectives on the level of evidence required in experimental studies of cellular therapies before proceeding with clinical trials of SCI. We conducted a survey of 27 SCI researchers actively involved in either preclinical and/or clinical research of cellular interventions for SCI, and then held a focus group meeting to facilitate more in-depth discussion around a number of translational issues. These included: the use of animal models, the use of injury models and mechanisms, the window for demonstrating efficacy, independent replication, defining "relevant, meaningful efficacy" in preclinical studies, and the expectation of therapeutic benefits for cellular interventions. Here we present the key findings from both the survey and focus group meeting in order to summarize and underscore the areas of consensus and disagreement amongst the s led researchers. It is anticipated that the knowledge generated from this initiative will help to incite future scientific discussions and expert guidelines towards translation of a cell therapy for persons with SCI.

Changing Pax6 expression correlates with axon outgrowth and restoration of topography during optic nerve regeneration

Publisher: Elsevier BV

Date: 2021

DOI: 10.1016/J.NEUROSCIENCE.2006.07.057

Abstract: Pax6, a member of the highly conserved developmental Pax gene family, plays a crucial role in early eye development and continues to be expressed in adult retinal ganglion cells (RGCs). Here we have used Western blots and immunohistochemistry to investigate the expression of Pax6 in the formation and refinement of topographic projections during optic nerve regeneration in zebrafish and lizard. In zebrafish with natural (12-h light/dark cycle) illumination, Pax6 expression in RGCs was decreased during axon outgrowth and increased during the restoration of the retinotectal map. Rearing fish in stroboscopic illumination to prevent retinotopic refinement resulted in a prolonged decrease in Pax6 levels return to natural light conditions resulted in map refinement and restoration of normal Pax6 levels. In lizard, RGC axons spontaneously regenerate but remain in a persistent state of regrowth and do not restore topography visual training during regeneration, however, allows a stabilization of connections and return of topography. Pax6 was persistently decreased in untrained animals but remained increased in trained ones. In both species, changes in expression were not due to cell ision or cell death. The results suggest that decreased Pax6 expression is permissive for axon regeneration and extensive searching, while higher levels of Pax6 are associated with restoration of topography.

Anatomical comparison of the macaque and marsupial visual cortex : common features that may reflect retention of essential cortical elements.

Publisher: Wiley

Date: 02-11-1998

DOI: 10.1002/(SICI)1096-9861(19981102)400:4<449::AID-CNE2>3.0.CO;2-A

Abstract: This study identifies fundamental anatomical features of primary visual cortex, area V1 of macaque monkey cerebral cortex, i.e., features that are present in area V1 of phylogenetically distant mammals of quite different lifestyle and features that are common to other regions of cortex. We compared anatomical constituents of macaque V1 with V1 of members of the two principal marsupial lines, the dunnart and the quokka, that erged from the eutherian mammalian line over 135 million years ago. Features of V1 common to both macaque and marsupials were then compared with anatomical features we have previously described for macaque prefrontal cortex. Despite large differences in overall area and thickness of V1 cortex between these animals, the absolute size of pyramidal neurons is remarkably similar, as are their specific dendritic branch patterns and patterns of distribution of intrinsic axons. Pyramidal neuron patchy connections exist in the supragranular V1 in both the marsupial quokka and macaque as well as in macaque prefrontal cortex. Several specific types of aspinous interneurons are common to area V1 in both marsupial and macaque and are also present in macaque prefrontal cortex. Spiny stellate cells are a common feature of the thalamic-recipient, mid-depth lamina 4 of V1 in all three species. Because these similarities exist despite the very different lifestyles and evolutionary histories of the animals compared, this finding argues for a highly conserved framework of cellular detail in macaque primary visual cortex rather than convergent evolution of these features.

Factors influencing thigh muscle volume change with cycling exercises in acute spinal cord injury–a secondary analysis of a randomized controlled trial

Publisher: Informa UK Limited

Date: 24-09-2022

DOI: 10.1080/10790268.2020.1815480

Iron Oxide-Induced Thermal Effects on Solid-State Upconversion Emissions in NaYF₄:Yb,Er Nanocrystals

Publisher: American Chemical Society (ACS)

Date: 13-08-2013

DOI: 10.1021/AM401837H

Abstract: Multifunctional materials exhibiting photon upconversion show promising applications for biological imaging and sensing. In this study, we examine the solid-state upconversion emission of NaYF4:Yb,Er nanoparticles in the presence of iron oxide nanoparticles. Fe3O4 nanoparticles (6 nm) were mixed with NaYF4:Yb,Er nanoparticles (either 10 or 50 nm) in varying proportions by drying chloroform solutions of nanoparticles onto glass slides. Upconversion spectra were acquired, and a laser power-dependent emission was observed and correlated with the iron oxide content in the mixture. Changes in the lattice temperature of the upconverting particles were monitored by careful observation of the relative intensities of the (2)H11/2 and (4)S3/2 →( 4)I15/2 transitions. The emission characteristics observed are consistent with an iron oxide-induced thermal effect that is dependent on both the laser power and the proportion of iron oxide. The results highlight that the thermal effects of mixed nanoparticle systems should be considered in the design of luminescent upconverting hybrid materials.

Changes in subtypes of Ca microdomains following partial injury to the central nervous system

Publisher: Oxford University Press (OUP)

Date: 2014

DOI: 10.1039/C3MT00336A

Abstract: Nanoscale secondary ion mass spectrometry demonstrates that subsets of Ca microdomains rapidly decrease after central nervous system injury.

An improved assay for the spectrophotometric determination of chondroitinase ABC activity

Publisher: Royal Society of Chemistry (RSC)

Date: 2013

DOI: 10.1039/C3NJ00168G

Lateralized predatory responses in the ornate dragon lizard (Ctenophorus ornatus)

Publisher: Ovid Technologies (Wolters Kluwer Health)

Date: 05-2005

DOI: 10.1097/00001756-200505310-00014

Abstract: Lateralized responses for visually elicited feeding behaviour have been reported in toads and birds but not in the phylogenetically intermediate class of vertebrates, the reptiles. Here we examined small social groups of ornate dragon lizards Ctenophorus ornatus (family Agamidae) and provide the first report in reptiles of right eye lateralization (left brain hemisphere) for predatory responses to prey. However, right eye lateralization was not evident initially but became stronger with time supporting a shift to right eye lateralization as the prey became increasingly familiar. The study is in agreement with recent findings in toads, adding credence to the hypothesis that lateralization originated in an early ancestor and highlighting the supposition that the strength and direction of lateralization is dependent on experience.

Transient up-regulation of retinal EphA3 and EphA5, but not ephrin-A2, coincides with re-establishment of a topographic map during optic nerve regeneration in goldfish

Publisher: Elsevier BV

Date: 10-2003

DOI: 10.1016/S0014-4886(03)00211-5

Abstract: Eph tyrosine kinase receptors and their ligands, the ephrins, play a key role in the establishment of retinotectal topography during development. Tectal up-regulation of ephrin-A2 in goldfish, coincident with the reestablishment of a retinotectal map, suggests a similar role during optic nerve regeneration. Here we report a complementary study of EphA3, EphA5 and ephrin-A2 expression in the retina. EphA3 and EphA5 are transiently up-regulated as ascending naso-temporal gradients, whereas ephrin-A2 remains uniform. The expression profiles differ from those in developing chick and mouse, suggesting that different combinations of retinal Eph receptors and ligands can generate topographic guidance information.

Recovery of whisking function after manual stimulation of denervated vibrissal muscles requires brain-derived neurotrophic factor and its receptor tyrosine kinase B

Publisher: Elsevier BV

Date: 09-2010

DOI: 10.1016/J.NEUROSCIENCE.2010.06.053

Abstract: Functional recovery following facial nerve injury is poor. Neuromuscular junctions (NMJs) are "bridged" by terminal Schwann cells and numerous regenerating axonal sprouts. We have shown that this poly-innervation of NMJs can be reduced by manual stimulation (MS) with restoration of whisking function. In addition, we have recently reported that insulin-like growth factor-1 (IGF-1) is required to mediate the beneficial effects of MS. Here we extend our findings to brain derived neurotrophic factor (BDNF). We then examined the effect of MS after facial-facial anastomosis (FFA) in heterozygous mice deficient in BDNF (BDNF(+/-)) or in its receptor TrkB (TrkB(+/-)). We quantified vibrissal motor performance and the percentage of NMJ bridged by S100-positive terminal Schwann cells. In intact BDNF(+/-) or TrkB(+/-) mice and their wild type (WT) littermates, there were no differences in vibrissal whisking nor in the percentage of bridged NMJ (0% in each genotype). After FFA and handling alone (i.e. no MS) in WT animals, vibrissal whisking litude was reduced (60% lower than intact) and the percentage of bridged NMJ increased (27% more than intact). MS improved both the litude of vibrissal whisking (not significantly different from intact) and the percentage of bridged NMJ (11% more than intact). After FFA and handling in BDNF(+/-) or TrkB(+/-) mice, whisking litude was again reduced (53% and 60% lower than intact) and proportion of bridged NMJ increased (24% and 29% more than intact). However, MS failed to improve outcome in both heterozygous strains (whisking litude 55% and 58% lower than intact proportion of bridged NMJ 27% and 18% more than intact). We conclude that BDNF and TRkB are required to mediate the effects of MS on target muscle reinnervation and recovery of whisking function.

Early In Vivo Changes in Calcium Ions, Oxidative Stress Markers, and Ion Channel Immunoreactivity Following Partial Injury to the Optic Nerve

Publisher: Wiley

Date: 31-10-2012

DOI: 10.1002/JNR.22784

Abstract: CNS injury is often localized but can be followed by more widespread secondary degenerative events that usually result in greater functional loss. Using a partial transection model in rat optic nerve (ON). we recently demonstrated in vivo increases in the oxidative stress-associated enzyme MnSOD 5 min after injury. However, mechanisms by which early oxidative stress spreads remain unclear. In the present study, we assessed ion distributions, additional oxidative stress indicators, and ion channel immunoreactivity in ON in the first 24 hr after partial transection. Using nanoscale secondary ion mass spectroscopy (NanoSIMS), we demonstrate changes in the distribution pattern of Ca ions following partial ON transection. Regions of elevated Ca ions in normal ON in vivo rapidly decrease following partial ON transection, but there is an increasingly punctate distribution at 5 min and 24 hr after injury. We also show rapid decreases in catalase activity and later increases in immunoreactivity of the advanced glycation end product carboxymethyl lysine in astrocytes. Increased oxidative stress in astrocytes is accompanied by significantly increased immunoreactivity of the AMPA receptor subunit GluR1 and aquaporin 4 (AQP4). Taken together, the results indicate that Ca ion changes and oxidative stress are early events following partial ON injury that are associated with changes in GluR1 AMPA receptor subunits and altered ionic balance resulting from increased AQP4.

Poly(glycidyl methacrylate) coated dual mode upconverting nanoparticles for neuronal cell imaging

Publisher: Royal Society of Chemistry (RSC)

Date: 2016

DOI: 10.1039/C5NJ03368C

Abstract: NaGdF 4 :Yb,Er nanoparticles with a functional poly(glycidyl methacrylate) (PGMA) coating, as a biocompatible multimodal formulation for neuronal cell imaging.

Fetal sciatic nerve growth is delayed following repeated maternal injections of corticosteroid in sheep

Publisher: Walter de Gruyter GmbH

Date: 10-01-2000

DOI: 10.1515/JPM.2000.004

Elucidating the Inability of Functionalized Nanoparticles to Cross the Blood–Brain Barrier and Target Specific Cells in Vivo

Publisher: American Chemical Society (ACS)

Date: 31-05-2019

DOI: 10.1021/ACSAMI.9B01356

Abstract: The adsorption of serum proteins on the surface of nanoparticles (NPs) delivered into a biological environment has been known to alter NP surface properties and consequently their targeting efficiency. In this paper, we use random copolymer (p(HEMA- ran-GMA))-based NPs synthesized using 2-hydroxyethyl methacrylate (HEMA) and glycidyl methacrylate (GMA). We show that serum proteins bind to the NP and that functionalization with antibodies and peptides designed to facilitate NP passage across the blood-brain barrier (BBB) to bind specific cell types is ineffective. In particular, we use systematic in vitro and in vivo analyses to demonstrate that p(HEMA- ran-GMA) NPs functionalized with HIV-1 trans-activating transcriptor peptide (known to cross the BBB) and α neural/glial antigen 2 (NG2) (known for targeting oligodendrocyte precursor cells (OPCs)), in idually and in combination, do not specifically target OPCs and are unable to cross the BBB, likely due to the serum protein binding to the NPs.

Barriers to Physical Activity In Individuals with Spinal Cord Injury: A Western Australian Study – Corrigendum

Publisher: Cambridge University Press (CUP)

Date: 13-07-2012

DOI: 10.1017/JRC.2012.10

Specific combinations of ion channel inhibitors reduce excessive Ca²⁺influx as a consequence of oxidative stress and increase neuronal and glial cell viability in vitro

Publisher: Elsevier BV

Date: 12-2016

DOI: 10.1016/J.NEUROSCIENCE.2016.10.005

Abstract: Combinations of Ca

Burn injury has a systemic effect on reinnervation of skin and restoration of nociceptive function

Publisher: Wiley

Date: 24-04-2012

DOI: 10.1111/J.1524-475X.2012.00787.X

Paranode Abnormalities and Oxidative Stress in Optic Nerve Vulnerable to Secondary Degeneration: Modulation by 670 nm Light Treatment

Publisher: Public Library of Science (PLoS)

Date: 19-06-2013

DOI: 10.1371/JOURNAL.PONE.0066448

Early exercise after spinal cord injury (‘Switch-On’): study protocol for a randomised controlled trial

Publisher: Springer Science and Business Media LLC

Date: 07-01-2015

DOI: 10.1186/1745-6215-16-7

Early rapid neurological assessment for acute spinal cord injury trials

Publisher: Mary Ann Liebert Inc

Date: 11-2016

DOI: 10.1089/NEU.2015.4360

Abstract: Clinical trials evaluating early therapies after spinal cord injury (SCI) are challenging because of the absence of a rapid assessment. The aim of this study was to determine whether the severity and level of SCI could be established from a brief neurological assessment capable of being used in an emergency setting. A brief assessment called the SPinal Emergency Evaluation of Deficits (SPEED) was developed and retrospectively evaluated in a cohort of 118 patients with SCI. Foot motor and sensory function was used to indicate injury severity. C3 dermatome sensation, handgrip strength and location of spinal pain were used to indicate the level of injury. With regard to injury severity, a high proportion of patients (94%) with no foot movement at the time of injury were initially diagnosed as motor complete (American Spinal Injury Association Impairment Scale [AIS] grade A-B), whereas all patients with foot movement were identified as motor incomplete (AIS grade C-D). This was reflected by a good correlation (r

Manually-stimulated recovery of motor function after facial nerve injury requires intact sensory input

Publisher: Elsevier BV

Date: 05-2008

DOI: 10.1016/J.EXPNEUROL.2008.02.019

Abstract: We have recently shown in rat that daily manual stimulation (MS) of vibrissal muscles promotes recovery of whisking and reduces polyinnervation of muscle fibers following repair of the facial nerve (facial-facial anastomosis, FFA). Here, we examined whether these positive effects were: (1) correlated with alterations of the afferent connections of regenerated facial motoneurons, and (2) whether they were achieved by enhanced sensory input through the intact trigeminal nerve. First, we quantified the extent of total synaptic input to motoneurons in the facial nucleus using synaptophysin immunocytochemistry following FFA with and without subsequent MS. We found that, without MS, this input was reduced compared to intact animals. The number of synaptophysin-positive terminals returned to normal values following MS. Thus, MS appears to counteract the deafferentation of regenerated facial motoneurons. Second, we performed FFA and, in addition, eliminated the trigeminal sensory input to facial motoneurons by extirpation of the ipsilateral infraorbital nerve (IONex). In this paradigm, without MS, vibrissal motor performance and pattern of end-plate reinnervation were as aberrant as after FFA without MS. MS did not influence the reinnervation pattern after IONex and functional recovery was even worse than after IONex without MS. Thus, when the sensory system is intact, MS restores normal vibrissal function and reduces the degree of polyinnervation. When afferent inputs are abolished, these effects are eliminated or even reversed. We conclude that rehabilitation strategies must be carefully designed to take into account the extent of motor and/or sensory damage.

Regulation of human PAX6 expression by miR-7

Publisher: SAGE Publications

Date: 2014

DOI: 10.4137/EBO.S13739

Abstract: The paired box gene 6 ( PAX6) is a powerful mediator of eye and brain organogenesis whose spatiotemporal expression is exquisitely controlled by multiple mechanisms, including post-transcriptional regulation by microRNAs (miRNAs). In the present study, we use bioinformatic predictions to identify three candidate microRNA-7 (miR-7) target sites in the human PAX6 3′ untranslated region (3′-UTR) and demonstrate that two of them are functionally active in a human cell line. Furthermore, transient transfection of cells with synthetic miR-7 inhibits PAX6 protein expression but does not alter levels of PAX6 mRNA, suggesting that miR-7 induces translational repression of PAX6. Finally, a comparison of PAX6 3′-UTRs across species reveals that one of the functional miR-7 target sites is conserved, whereas the second functional target site is found only in primates. Thus, the interaction between PAX6 and miR-7 appears to be highly conserved however, the precise number of sites through which this interaction occurs may have expanded throughout evolution.

SCIPA Switch-On

Publisher: SAGE Publications

Date: 09-03-2017

DOI: 10.1177/1545968317697035

Abstract: Background. Substantial skeletal muscle atrophy after spinal cord injury (SCI) carries significant repercussions for functional recovery and longer-term health. Objective. To compare the efficacy, safety, and feasibility of functional electrical stimulation–assisted cycling (FESC) and passive cycling (PC) to attenuate muscle atrophy after acute SCI. Methods. This multicenter, assessor-blinded phase I/II trial randomized participants at 4 weeks post-SCI to FESC or PC (4 sessions per week, 1 hour maximum per session, over 12 weeks). The primary outcome measure was mean maximum cross-sectional area (CSA) of thigh and calf muscles (magnetic resonance imaging), and secondary outcome measures comprised body composition (dual energy X-ray absorptiometry), anthropometry, quality of life, and adverse events (AEs). Results. Of 24 participants, 19 completed the 12-week trial (10 FESC, 9 PC, 18 male). Those participants completed % of training sessions (FESC, 83.5% PC, 85.9%). No significant between-group difference in postintervention muscle CSA was found. No significant between-group difference was found for any other tissue, anthropometric parameter, or behavioral variable or AEs. Six participants experienced thigh hypertrophy (FESC = 3 PC = 3). Atrophy was attenuated ( %) in 15 cases (FESC = 7 PC = 8). Conclusions. Both cycle ergometry regimens examined were safe, feasible, and well tolerated early after SCI. No conclusions regarding efficacy can be drawn from our data. Further investigation of both modalities early after SCI is required.

SCIPA Com: Outcomes from the spinal cord injury and physical activity in the community intervention

Publisher: Springer Science and Business Media LLC

Date: 19-01-2016

DOI: 10.1038/SC.2015.235

Abstract: Quasi-experimental translational study with pre- and post-measures. To determine the effects of the Spinal Cord Injury and Physical Activity in the Community (SCIPA Com) intervention on leisure-time physical activity (LTPA) and associated outcomes among participants with spinal cord injury (SCI). Young Men's Christian Associations and community fitness centers, Australia and New Zealand. SCIPA Com consisted of three stages: (i) training exercise professionals via the Train the Trainers Spinal Cord Injury course (ii) implementation of supervised physical activity programs twice a week for 30 to 60 min for 8 to 12 weeks and (iii) follow-up assessments on health outcomes over 9 months. Participants with SCI were classified as active or inactive by baseline LTPA levels and linear mixed methods compared LTPA between groups over time. Sixty-four community-dwelling participants with SCI completed customized physical activity programs. Compared with baseline, there were significant improvements in LTPA (26 min per day, 95% confidence interval (CI): 16.6-35.4 P<0.001), functional goals (2, 95% CI: 1.72-2.37 P<0.001), self-esteem (1.5, 95% CI: 0.72-2.27 P<0.001) and overall quality of life (P<0.05). Over time, LTPA participation was greater among the active compared with the inactive group, although LTPA levels among the inactive improved compared with baseline. Significant improvements in LTPA participation and health outcomes were observed, especially among inactive in iduals with SCI. SCIPA Com is an ecologically valid intervention based on training and support provided to community exercise professionals who, although new to adapted training, delivered effective physical activity programs for those at risk of inactivity. Transport Accident Commission (Project Number DP172) and the International Postgraduate Research Scholarship (IPRS), Curtin University.

Ephrin-B2 immunoreactivity distribution in adult mouse brain

Publisher: Elsevier BV

Date: 11-2007

DOI: 10.1016/J.BRAINRES.2007.08.065

Abstract: Ephrin ligands and their receptors Eph receptor tyrosine-kinases have received extensive attention for their multiple key roles during development, particularly in the central nervous system (CNS). For ex le, at early stages of brain and spinal cord development, membrane-bound ephrins provide signals that direct migrating cells and axons. However, much less is known about the role of ephrins and Eph receptors in the adult CNS. Here, we investigated the distribution of ephrin-B2 protein expression in the adult mouse brain to gain insight into its possible function(s). We show that ephrin-B2 is expressed in areas with high levels of synaptic plasticity, such as the cerebral cortex, hippoc us and cerebellum. However, at the cellular level, ephrin-B2 was localized to neuronal cell bodies rather than to the dendritic synaptic sites where mechanisms of long-term modifications of excitatory transmission are located. Our results suggest a role for ephrin-B2 in the membrane at the cell body, possibly in relation to axonal-somatic inhibitory synapses.

In vivo imaging and biodistribution of multimodal polymeric nanoparticles delivered to the optic nerve

Publisher: Wiley

Date: 13-03-2012

DOI: 10.1002/SMLL.201102648

Abstract: The use of nanoparticles for targeted delivery of therapeutic agents to sites of injury or disease in the central nervous system (CNS) holds great promise. However, the biodistribution of nanoparticles following in vivo administration is often unknown, and concerns have been raised regarding potential toxicity. Using poly(glycidyl methacrylate) (PGMA) nanoparticles coated with polyethylenimine (PEI) and containing superparamagnetic iron oxide nanoparticles as a magnetic resonance imaging (MRI) contrast agent and rhodamine B as a fluorophore, whole animal MRI and fluorescence analyses are used to demonstrate that these nanoparticles (NP) remain close to the site of injection into a partial injury of the optic nerve, a CNS white matter tract. In addition, some of these NP enter axons and are transported to parent neuronal somata. NP also remain in the eye following intravitreal injection, a non-injury model. Considerable infiltration of activated microglia/macrophages occurs in both models. Using magnetic concentration and fluorescence visualization of tissue homogenates, no dissemination of the NP into peripheral tissues is observed. Histopathological analysis reveals no toxicity in organs other than at the injection sites. Multifunctional nanoparticles may be a useful mechanism to deliver therapeutic agents to the injury site and somata of injured CNS neurons and thus may be of therapeutic value following brain or spinal cord trauma.

Manual stimulation of the whisker pad after hypoglossal–facial anastomosis (HFA) using a Y-tube conduit does not improve recovery of whisking function

Publisher: Springer Science and Business Media LLC

Date: 13-03-2014

DOI: 10.1007/S00221-014-3892-2

Abstract: Facial nerve injury is a common clinical trauma involving long-term functional deficits with facial asymmetry leading to associated psychological issues and social hardship. We have recently shown that repair by hypoglossal-facial or facial-facial nerve surgical end-to-end anastomosis and suture [hypoglossal-facial anastomosis (HFA) or facial-facial anastomosis (FFA)] results in collateral axonal branching, polyinnervation of neuromuscular junctions (NMJs) and poor function. We have also shown that another HFA repair procedure using an isogenic Y-tube (HFA + Y-tube) and involving a 10-mm gap reduces collateral axonal branching, but fails to reduce polyinnervation. Furthermore, we have previously demonstrated that manual stimulation (MS) of facial muscles after FFA or HFA reduces polyinnervation of NMJs and improves functional recovery. Here, we examined whether HFA + Y-tube and MS of the vibrissal muscles reduce polyinnervation and restore function. Isogenic Y-tubes were created using abdominal aortas. The proximal hypoglossal nerve was inserted into the long arm and sutured to its wall. The distal zygomatic and buccal facial nerve branches were inserted into the two short arms and likewise sutured to their walls. Manual stimulation involved gentle stroking of the vibrissal muscles by hand mimicking normal whisker movement. We evaluated vibrissal motor performance using video-based motion analysis, degree of collateral axonal branching using double retrograde labeling and the quality of NMJ reinnervation in target musculature using immunohistochemistry. MS after HFA + Y-tube reduced neither collateral branching, nor NMJ polyinnervation. Accordingly, it did not improve recovery of function. We conclude that application of MS after hypoglossal-facial nerve repair using an isogenic Y-tube is contraindicated: it does not lead to functional recovery but, rather, worsens it.

Retinal ganglion cell axons regenerate in the presence of intact sensory fibres

Publisher: Ovid Technologies (Wolters Kluwer Health)

Date: 02-2006

DOI: 10.1097/01.WNR.0000195668.07467.A8

Abstract: A novel allograft paradigm was used to test whether adult mammalian central axons regenerate within a peripheral nerve environment containing intact sensory axons. Retinal ganglion cell axon regeneration was compared following anastomosis of dorsal root ganglia grafts or conventional peripheral nerve grafts to the adult rat optic nerve. Dorsal root ganglia grafts comprised intact sensory and degenerate motor axons, whereas conventional grafts comprised both degenerating sensory and motor axons. Retinal ganglion cell axons were traced after 2 months. Dorsal root ganglia survived with their axons persisting throughout the graft. Comparable numbers of retinal ganglion cells regenerated axons into both dorsal root ganglia (1053+/-223) and conventional grafts (1323+/-881 P>0.05). The results indicate that an intact sensory environment supports central axon regeneration.

Axon order in the visual pathway of the quokka wallaby

Publisher: Wiley

Date: 19-01-1998

DOI: 10.1002/(SICI)1096-9861(19980119)390:3<333::AID-CNE3>3.0.CO;2-2

Abstract: Axon order throughout the visual pathway of the quokka wallaby (Setonix brachyurus) was determined after localised retinal applications of the tracers DiI and/or DiASP. Postnatal days (P) 22-90 were studied to encompass the development and refinement of retinal projections. Order was essentially similar at all stages. Axons entered the optic nerve head true to their sector of retinal origin. In the optic nerve, nasal and temporal axons continued to reflect their retinal origin, dominating, respectively, the medial and lateral halves. By contrast, dorsal and ventral axons exchanged locations between the retrobulbar level and one-third the distance along the nerve thus, the inversion of the dorsoventral retinal axis, imposed by the lens, was corrected. Decussating axons maintained their relative locations through the chiasm. At the base of the optic tract, nasal and temporal axons underwent an axial rotation to lie on the medial and lateral sides, respectively thus nasal overlapped with ventral axons and temporal with dorsal axons. Axons maintained their alignments throughout the tract, and as a result, nasal and ventral axons invaded the superior colliculus medially, whereas temporal and dorsal axons invaded laterally. Each retinal quadrant terminated preferentially in its retinotopically appropriate sector of the colliculus. The arrangement of axons in the quokka visual pathway displays several novel features. Axon order is distinct throughout, involving a well-demarcated exchange of dorsal and ventral axons in the nerve and an axial rotation of nasal and temporal axons at the base of the tract these relocations suggest decision regions for growing axons. The organisation presumably underlies the less extensive searching within the developing superior colliculus to generate retinotopic maps in the quokka and also in tammar wallaby [Marotte, J. Comp Neurol. 293:524-539, 1990] than in the rat [Simon and O'Leary, J. Neurosci. 12:1212-1232, 1992].

PSA-NCAM is up-regulated during optic nerve regeneration in lizard but not in goldfish

Publisher: Elsevier BV

Date: 07-2003

DOI: 10.1016/S0014-4886(03)00081-5

Abstract: The addition of polysialic acid (PSA) to neural cell adhesion molecule (NCAM) facilitates axon growth. Here we use Western blots and immunohistochemistry to examine expression of PSA-NCAM during optic nerve regeneration. In lizard, retinal ganglion cell axons become transiently PSA-NCAM positive. By contrast, goldfish RGC axons are PSA-NCAM negative both in normal animals and throughout regeneration with the exception of a PSA-NCAM-positive fascicle arising from newly generated RGCs. Transient sialylation of NCAM in lizard may assist regeneration in the nonpermissive reptilian visual pathway and facilitate the reestablishment of a crude topographic map down-regulation in the long term may contribute to the breakdown in topography. The lack of sialylation in goldfish presumably reflects the permissive nature of the substrate allowing axon regeneration and the successful reestablishment of a topographic map.

Reinnervation of the Superior Colliculus Delays Down-regulation of Ephrin A2 in Neonatal Rat

Publisher: Elsevier BV

Date: 08-2001

DOI: 10.1006/EXNR.2001.7722

Retinal Structure and Visual Acuity in a Polyprotodont Marsupial, the Fat-Tailed Dunnart (Sminthopsis crassicaudata)

Publisher: S. Karger AG

Date: 1999

DOI: 10.1159/000006588

Abstract: The visual system of the fat-tailed dunnart i (Sminthopsis crassicaudata), /i a small polyprotodont marsupial, has been examined both anatomically and behaviourally. The ganglion cell layer was examined in cresyl-violet stained wholemounts and found to contain a mean of 81,400 ganglion cells (SD ± 3,360) the identification of ganglion cells was supported by a correspondence to optic axon counts. Ganglion cells were distributed as a mid-temporally situated area centralis, embedded in a pronounced visual streak. Localised implants of horseradish peroxidase into retinal wholemounts revealed both A-type and B-type horizontal cells. Sections of the outer retina showed it to be rod-dominated, with a rod-to-cone ratio of 40:1 at the area centralis cones were found to contain oil droplets but double cones were not a prominent feature. The retinal pigment epithelium consisted of squamous cells. Visual acuity, estimated from counts of peak ganglion cell density (8,300/mm sup /sup , SD ± 1,180) and measurements of posterior nodal distance (2.9 mm), was found to be 2.30 cycles per degree. The value was close to that of 2.36 cycles per degree estimated by behavioural tests using a Mitchell jumping stand values were similar at low, intermediate and high light levels. Our findings are discussed in relation to the lifestyle of the dunnart.

Erratum

Publisher: Elsevier BV

Date: 10-2017

DOI: 10.1016/J.JPHYS.2017.08.005

Abstract: What is the effect of adding an intensive task-specific hand-training program involving functional electrical stimulation to a combination of usual care plus three 15-minute sessions per week of one-to-one hand therapy in people with sub-acute tetraplegia? A parallel group, randomised, controlled trial. Participants were randomly assigned (1:1) via a computer-generated concealed block randomisation procedure to either a control or experimental intervention. Seventy people with C2 to T1 motor complete or incomplete tetraplegia within 6 months of injury. Participants were recruited from seven spinal units in Australia and New Zealand. Experimental participants received intensive training for one hand. Intensive training consisted of training with an instrumented exercise workstation in conjunction with functional electrical stimulation for 1hour per day, 5 days per week for 8 weeks. Both groups received usual care and 15minutes of one-to-one hand therapy three times per week without functional electrical stimulation. The primary outcome was the modified Action Research Arm Test reflecting arm and hand function, which was assessed at the end of the intervention, that is, 11 weeks after randomisation. Secondary outcomes were measured at 11 and 26 weeks. Sixty-six (94%) participants completed the post-intervention assessment and were included in the primary intention-to-treat analysis. The mean (SD) modified Action Research Arm Test score for experimental and control participants at the post-intervention assessment was 36.5 points (SD 16.0) and 33.2 points (SD 17.5), respectively, with an adjusted mean between-group difference of 0.9 points (95% CI -4.1 to 5.9). Adding an intensive task-specific hand-training program involving functional electrical stimulation to a combination of usual care plus three 15-minute sessions per week of one-to-one hand therapy does not improve hand function in people with sub-acute tetraplegia. Australian and New Zealand Trial Registry ACTRN12609000695202 and ClinicalTrials.gov NCT01086930. [Harvey LA, Dunlop SA, Churilov L, Galea MP, Spinal Cord Injury Physical Activity (SCIPA) Hands On Trial Collaborators (2017) Early intensive hand rehabilitation is not more effective than usual care plus one-to-one hand therapy in people with sub-acute spinal cord injury ('Hands On'): a randomised trial. Journal of Physiotherapy 63: 197-204].

Segregation of optic input in a three-eyed mammal

Publisher: Elsevier BV

Date: 02-1996

DOI: 10.1006/EXNR.1996.0028

Abstract: Using a marsupial mouse, we have transplanted additional eye primordia to the midbrain at stages before host visual centers are normally innervated transplant or host projections were later traced. In contrast to the normally continuous crossed retinocollicular input, both transplant and host projections were arranged as rostrocaudally aligned stripes or as discrete patches. We propose that competitive interactions between transplant and host axons have induced the discontinuous input.

Eph/ephrin expression in the adult rat visual system following localized retinal lesions: localized and transneuronal up‐regulation in the retina and superior colliculus

Publisher: Wiley

Date: 10-2005

DOI: 10.1111/J.1460-9568.2005.04381.X

Abstract: Following unilateral optic nerve section in adult PVG hooded rat, the axon guidance cue ephrin-A2 is up-regulated in caudal but not rostral superior colliculus (SC) and the EphA5 receptor is down-regulated in axotomised retinal ganglion cells (RGCs). Changes occur bilaterally despite the retino-collicular projection being mostly crossed. Here we investigate the dynamics of Eph/ephrin expression using in situ hybridization and semi-quantitative immunohistochemistry after localized retinal lesions. Unilateral krypton laser lesions to dorso-nasal retina ablated contralaterally projecting RGCs (DN group) ventro-temporal lesions ablated contralaterally and ipsilaterally projecting RGCs (VT group). Lesions of the entire retina served as controls (Total group). Results are compared to normal animals in which tectal ephrin-A2 and retinal EphA5 are expressed, respectively, as shallow ascending rostro-caudal and naso-temporal gradients. In both SCs of DN and Total groups, tectal ephrin-A2 was up-regulated caudally in the VT group, expression remained normal bilaterally. Unilateral collicular ablation indicated that bilateral changes in ephrin-A2 expression are mediated via intercollicular pathways. EphA5 expression in the VT group was elevated in the intact nasal region of experimental retinae. For each experimental group, EphA5 expression was also elevated in nasal retina of the opposite eye, resulting in uniform expression across the naso-temporal axis. Up-regulation of ephrin-A2 in caudal, but not rostral, SC suggests the enhancement of developmental positional information as a result of injury. Bilateral increases in retinal EphA5 expression demonstrate that signals for up-regulation operate interocularly. The study demonstrates that signals regulating guidance cue expression are both localized and relayed transneuronally.

Achieving assessor accuracy on the International Standards for Neurological Classification of Spinal Cord Injury

Publisher: Springer Science and Business Media LLC

Date: 20-06-2017

DOI: 10.1038/SC.2017.67

Abstract: A retrospective audit of assessor accuracy using the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) in three multicentre randomised controlled trials (SCIPA: Spinal Cord Injury and Physical Activity) spanning 2010-2014 with standards revised in 2011. To investigate assessor accuracy of neurological classification after spinal cord injury. Australia and New Zealand. ISNCSCI examinations were undertaken by trained clinicians prior to randomisation. Data were recorded manually and ISNCSCI worksheets circulated to panels, consensus reached and worksheets corrected. An audit team used a 2014 computerised ISNCSCI algorithm to check manual worksheets. A second audit team assessed whether the 2014 computerised algorithm accurately reflected pre- and post-2011 ISNCSCI standards. Of the 208 ISNCSCI worksheets, 24 were excluded. Of the remaining 184 worksheets, 47 (25.5%) were consistent with the 2014 computerised algorithm and 137 (74.5%) contained one or more errors. Errors were in motor (30.1%) or sensory (12.4%) levels, zone of partial preservation (24.0%), motor/sensory scoring (21.5%), ASIA Impairment Scale (AIS, 8.3%) and complete/incomplete classification (0.8%). Other difficulties included classification when anal contraction/sensation was omitted, incorrect neurological levels and violation of the 'motor follows sensory rule in non-testable myotomes' (7.4%). Panel errors comprised corrections that were incorrect or missed or incorrect changes to correct worksheets. Given inaccuracies in the manual ISNCSCI worksheets in this long-term clinical trial setting, continued training and a computerised algorithm are essential to ensure accurate scoring, scaling and classification of the ISNCSCI and confidence in clinical trials.

Repeated ultrasound guided fetal injections of corticosteroid alter nervous system maturation in the ovine fetus

Publisher: Walter de Gruyter GmbH

Date: 05-01-2001

DOI: 10.1515/JPM.2001.015

Single Nucleotide Polymorphisms Associated With Gut Homeostasis Influence Risk and Age-at-Onset of Parkinson's Disease

Publisher: Frontiers Media SA

Date: 17-11-2020

DOI: 10.3389/FNAGI.2020.603849

A dorso-ventral gradient of Pax6 in the developing retina suggests a role in topographic map formation

Publisher: Elsevier BV

Date: 02-2003

DOI: 10.1016/S0165-3806(02)00605-3

Abstract: Expression of the transcription factor Pax6 was assessed immunohistochemically in embryonic chick retina during retino-tectal map formation. A low dorsal to high ventral gradient was found that correlated with expression of the axonal guidance cue EphB2. Furthermore, transfection of Pax6 into undifferentiated P19 cells up-regulated EphB2. The results raise the possibility that Pax6 is upstream of EphB2 and that its graded expression defines the dorso-ventral axis of the retino-tectal projection.

Early intensive hand rehabilitation after spinal cord injury (“Hands On”): a protocol for a randomised controlled trial

Publisher: Springer Science and Business Media LLC

Date: 17-01-2011

DOI: 10.1186/1745-6215-12-14

A scoping review protocol on in vivo human plastic exposure and health impacts

Publisher: Cold Spring Harbor Laboratory

Date: 10-02-2022

DOI: 10.1101/2022.02.10.22270706

Abstract: Global plastic production has increased exponentially since the 1960s, with more than 6300 million metric tons of plastic waste generated to date. Studies have found a range of human health impacts associated with exposure to plastic chemicals. However, only a fraction of plastic chemicals used have been studied in vivo , and then often in animals, for acute toxicological effects. With many questions still unanswered about how long-term exposure to plastic impacts human health, there is an urgent need to map human in vivo research conducted to date, casting a broad net by searching terms for a comprehensive suite of plastic chemical exposures and the widest range of health domains. This protocol describes a scoping review that will follow the recommended framework outlined in 2017 Guidance for the Conduct of Joanna Briggs Institute (JBI) Scoping Reviews , to be reported in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) Checklist . A literature search of primary clinical studies in English from 1960 onwards will be conducted in MEDLINE (Ovid) and EMBASE (Ovid) databases. References eligible for inclusion will be identified through a quality-controlled, multi-level screening process. Extracted data will be presented in diagrammatic and tabular form, with a narrative summary addressing the review questions. This scoping review will comprehensively map the primary research undertaken to date on plastic exposure and human health. Secondary outputs will include extensive databases on plastic chemicals and human health outcomes/impacts. Open Science Framework (OSF)-Standard Pre-Data Collection Registration, osf.io/gbxps DOI: 10.17605/OSF.IO/GBXPS

Early intensive hand rehabilitation is not more effective than usual care plus one-to-one hand therapy in people with sub-acute spinal cord injury ('Hands On')

Publisher: Elsevier BV

Date: 10-2017

DOI: 10.1016/J.JPHYS.2017.08.006

Intensive exercise program after spinal cord injury ( Full-On): Study protocol for a randomized controlled trial

Publisher: Springer Science and Business Media LLC

Date: 2013

DOI: 10.1186/1745-6215-14-291

Early Vascular and Neuronal Changes in a VEGF Transgenic Mouse Model of Retinal Neovascularization

Publisher: Association for Research in Vision and Ophthalmology (ARVO)

Date: 10-2006

DOI: 10.1167/IOVS.06-0251

Abstract: To investigate early retinal changes in a vascular endothelial growth factor (VEGF) transgenic mouse (tr029VEGF rhodopsin promoter) with long-term damage that mimics nonproliferative diabetic retinopathy (NPDR) and mild proliferative diabetic retinopathy (PDR). Rhodopsin and VEGF expression was assessed up to postnatal day (P)28. Vascular and retinal changes were charted at P7 and P28 using sections and wholemounts stained with hematoxylin and eosin or isolectin IB4 Griffonia simplicifolia S les were examined using light, fluorescence, and confocal microscopy. Rhodopsin was detected at P5 and reached mature levels by P15 VEGF protein expression was transient, peaking at P10 to P15. In wild-type (wt) mice at P7, vessels had formed in the nerve fiber/retinal ganglion cell layer and showed a centroperipheral maturational gradient some capillaries had formed a second bed on the vitread side of the inner nuclear layer (INL). By P28, the retinal vasculature had three mature capillary beds, the third abutting the sclerad aspect of the INL. In tr029VEGF mice, capillary bed formation was accelerated compared with that in wt, with abnormal vessels extending to the sclerad side of the INL by P7 and abnormally penetrating the photoreceptors by P28. Compared with P7, vascular lesions were more numerous at P28 when capillary dropout was also evident. At both stages, retinal layers were thinned most where abnormal vessel growth was greatest. Concomitant damage to the vasculature and neural retina at early stages in tr029VEGF suggest that both tissues are affected, providing opportunities to examine early cellular events that lead to long-term disease.

The gut-brain axis and gut inflammation in Parkinson’s disease

Publisher: Informa UK Limited

Date: 05-05-2020

DOI: 10.1080/14728222.2020.1763956

Multimodal and multifunctional stealth polymer nanospheres for sustained drug delivery

Publisher: Royal Society of Chemistry (RSC)

Date: 2012

DOI: 10.1039/C2NJ40016B

Activity-dependent plasticity: implications for recovery after spinal cord injury

Publisher: Elsevier BV

Date: 08-2008

DOI: 10.1016/J.TINS.2008.05.004

Abstract: Spinal cord injury causes devastating loss of function and progressive, potentially life-threatening, secondary complications. Although significant preclinical advances continue to be made in cellular and molecular therapies which promote regeneration, plasticity within remaining circuits and how it can be influenced by physical activity is evolving as a key research area. Understanding what constitutes plasticity, and how activity shapes it, has centred primarily on neurons, but evidence is emerging that activity also influences glial cells. Basic and clinical research continue to advance our knowledge of the quality and quantity of physical exercise required to improve function, while mental exercise is emerging as another avenue. Increased understanding of mechanisms driving activity-dependent plasticity will help develop rehabilitative strategies which optimise functional recovery.

EphA5 and ephrin‐A2 expression during optic nerve regeneration: a ‘two‐edged sword’

Publisher: Wiley

Date: 02-2007

DOI: 10.1111/J.1460-9568.2007.05321.X

Abstract: During development, gradients of EphA receptors (nasal(low)-temporal(high)) and their ligands ephrin-As (rostral(low)-caudal(high)) are involved in establishing topography between retinal ganglion cells (RGCs) and the superior colliculus (SC). EphA5-expressing RGC axons are repulsed by ephrin-A2-expressing SC neurones. In adult rats RGCs maintain graded EphA5 expression but ephrin-A2 expression is down-regulated in the SC to a weak gradient. At 1 month after optic nerve transection, EphA5 expression is reduced in the few remaining RGCs and is no longer graded by contrast, SC ephrin-A2 is up-regulated to a rostral(low)-caudal(high) gradient. Here we examined expression in adult rat 1 month after bridging the retina and SC with a peripheral nerve graft, a procedure that enhances RGC survival and permits RGC axon regeneration. Double labelling with cell markers revealed preservation of a nasal(low)-temporal(high) EphA5 gradient in RGCs and establishment of a rostral(low)-caudal(high) ephrin-A2 gradient within neurones of the SC. The results suggest a potential for guidance cues to restore the topography of RGC axons in the SC. However, high ephrin-A2 levels were also found in astrocytes surrounding the peripheral nerve graft insertion site. The repulsive ephrin-A2 environment offers at least a partial explanation for the observation that only a limited number of RGC axons can exit the graft to enter target central nervous system tissue.

Culture conditions affect proliferative responsiveness of olfactory ensheathing glia to neuregulins

Publisher: Wiley

Date: 05-2007

DOI: 10.1002/GLIA.20502

Abstract: Olfactory ensheathing glia (OEG) have been used to improve outcome after experimental spinal cord injury and are being trialed clinically. Their rapid proliferation in vitro is essential to optimize clinical application, with neuregulins (NRG) being potential mitogens. We examined the effects of NRG-1beta, NRG-2alpha, and NRG3 on proliferation of p75-immunopurified adult OEG. OEG were grown in serum-containing medium with added bovine pituitary extract and forskolin (added mitogens) or in serum-containing medium (no added mitogens). Cultures were switched to chemically defined medium (no added mitogens or serum), NRG added and OEG proliferation assayed using BrdU. OEG grown initially with added mitogens were not responsive to added NRGs and pre-exposure to forskolin and pituitary extract increased basal proliferation rates so that OEG no longer responded to added NRG. However, NRG promoted proliferation but only if cells were initially grown in mitogen-free medium. Primary OEG express ErbB2, ErbB3, and small levels of ErbB4 receptors functional blocking indicates that ErbB2 and ErbB3 are the main NRG receptors utilized in the presence of NRG-1beta. The long-term stimulation of OEG proliferation by initial culture conditions raises the possibility of manipulating OEG before therapeutic transplantation.

Characterisation of tectal ephrin-A2 expression during optic nerve regeneration in goldfish: implications for restoration of topography

Publisher: Elsevier BV

Date: 06-2004

DOI: 10.1016/J.EXPNEUROL.2004.02.006

Neurite resposes to ephrin-A5 modulated by BDNF: Evidence for TrkB-EphA interactions

Publisher: Elsevier BV

Date: 10-2008

DOI: 10.1016/J.BBRC.2008.07.110

Abstract: In the developing visual system, growing retinal ganglion cell (RGC) axons are exposed to multiple guidance and growth factors. Furthermore, the relative levels of these factors are differentially regulated as topography is roughly established and then refined. We have shown that during the establishment of rough topography (P3), growth cones of pure and explanted RGCs treated with combinations of BDNF and ephrin-A5-Fc responded differently than RGCs treated with BDNF or ephrin-A5-Fc alone (p=0.0083). The response to the combined treatment mimicked that of RGCs cultured with ephrin-A5-Fc alone once topography refines. The guidance cue receptors EphA and TrkB were shown to co-localise in RGCs in vitro. Furthermore, EphA and TrkB receptors interacted directly in in vitro binding assays. Our results suggest that the conversion of growth cone responses from collapse to stabilisation as topography refines, occurs as a result of interactions between EphA and TrkB receptors.

Optimal Bladder Management Following Spinal Cord Injury: Evidence, Practice and a Cooperative Approach Driving Future Directions in Australia

Publisher: Elsevier BV

Date: 10-2018

DOI: 10.1016/J.APMR.2018.04.030

Abstract: We examined spinal cord injury (SCI) catheterization practices in Australia to understand practice patterns and consistency with research evidence. A national facilitated discussion forum was held during the annual Australian and New Zealand Spinal Cord Society conference attended by 66 conference delegates. Initially, presentations were given on the latest laboratory research examining bladder changes following SCI an overview of evidence-based recommendations indicating that intermittent catheterization is best practice and results of a single-center practice audit that demonstrated substantial delay in transition between acute SCI and intermittent catheterization. The ensuing discussion covered current catheterization practices in both inpatient SCI units and the community and highlighted gaps between evidence and practice, with considerable variation in practice between centers and settings. Reported challenges to implementing best practice included social, economic, and resource factors. A disconnect between hospital and community practice was also identified as an important barrier to long-term uptake of intermittent catheterization following acute SCI. The discussion identified 3 proposed activities: (1) explore current practice and bladder health following SCI in greater depth across SCI units and in local communities through audits and standardized biochemical analysis (2) determine the behavioral drivers of current practice and (3) develop a knowledge translation strategy to better align practice with current clinical practice guidelines.

Compensatory and transneuronal plasticity after early collicular lesions

Publisher: Wiley

Date: 20-12-2007

DOI: 10.1002/CNE.21221

Abstract: Plasticity within the visual system was assessed in the quokka wallaby following unilateral superior collicular (SC) ablation at postnatal days (P) 8-10, prior to the arrival of retinal ganglion cell (RGC) axons. At maturity (P100), projections were traced from the eye opposite the ablation, and total RGC numbers were estimated for both eyes. Ablations were partial (28-89% of SC remaining) or complete (0-5% of SC remaining). Projections to the visual centers showed significant bilateral (P 0.05). Compared with normal, total RGC numbers were significantly (P < 0.05) reduced in the eye opposite the ablation but increased (P 0.05). As in rodents, the visual system in quokka compensates following injury by maintaining a set volume of arborization but does so by forming only minor anomalous projections. Furthermore, increased RGC numbers in the eye ipsilateral to the lesion indicate that compensation occurs transneuronally, thus maintaining total numbers of projecting neurons. The implication is that the visual system acts in concert following unilateral injury to maintain set values for RGC terminal arbors as well as their cell bodies.

Metallothionein induces a regenerative reactive astrocyte phenotype via JAK/STAT and RhoA signalling pathways

Publisher: Elsevier BV

Date: 2010

DOI: 10.1016/J.EXPNEUROL.2009.10.006

Abstract: Following central nervous system injury, astrocytes rapidly respond by undergoing a stereotypical pattern of molecular and morphological alterations termed "reactive" astrogliosis. We have reported previously that metallothioneins (MTs) are rapidly expressed by reactive astrocytes and that their secretion and subsequent interaction with injured neurons leads to improved neuroregeneration. We now demonstrate that exogenous MT induces a reactive morphology and elevated GFAP expression in cultured astrocytes. Furthermore, these astrogliotic hallmarks were mediated via JAK/STAT and RhoA signalling pathways. However, rather than being inhibitory, MT induced a form of astrogliosis that was permissive to neurite outgrowth and which was associated with decreased chondroitin sulphate proteoglycan (CSPG) expression. The results suggest that MT has an important role in mediating permissive astrocytic responses to traumatic brain injury.

Accelerated low-intensity rTMS does not rescue anxiety behaviour or abnormal connectivity in young adult rats following chronic restraint stress

Publisher: Elsevier BV

Date: 09-2022

DOI: 10.1016/J.YNIRP.2022.100104

Myelin sheath decompaction, axon swelling, and functional loss during chronic secondary degeneration in rat optic nerve

Publisher: Association for Research in Vision and Ophthalmology (ARVO)

Date: 04-09-2012

DOI: 10.1167/IOVS.12-10080

Abstract: To examine chronic changes occurring at 6 months following partial optic nerve (ON) transection, assessing optic axons, myelin, and visual function. Dorsal ON axons were transected, leaving ventral optic axons vulnerable to secondary degeneration. At 3 and 6 months following partial transection, toluidine-blue stained sections were used to assess dimensions of the ON injury site. Transmission electron microscopy (TEM) images of ventral ON were used to quantify numbers, diameter, area, and myelin thickness of optic axons. Immunohistochemistry and fluoromyelin staining were used to assess semiquantitatively myelin protein, lipids in ventral ON, and retinal ganglion cells (RGCs) in midventral retina. Visuomotor function was assessed using optokinetic nystagmus. Following partial ON transection, optic axons and function remained disrupted at 6 months. Although ventral ON swelling observed at 3 months (P ≤ 0.05) receded to normal by 6 months, ultrastructurally, myelinated axons remained swollen (P ≥ 0.05), and myelin thickness increased (P ≤ 0.05) due to loosening of lamellae and an increase in the number of intraperiodic lines. Axons with decompacted myelin persisted and were distinguished as having large axonal calibers and thicker myelin sheaths. Nevertheless, progressive loss of myelin lipid staining with fluoromyelin was seen at 6 months. Despite no further loss of ventral optic axons between 3 and 6 months (P ≥ 0.05), visuomotor function progressively declined at 6 months following partial transection (P ≤ 0.05). Continued decompaction of myelin, altered myelin structure, and swelling of myelinated axons are persistent features of the chronic phases of secondary degeneration and likely contribute to progressive loss of visual function.

Enabling dual cellular destinations of polymeric nanoparticles for treatment following partial injury to the central nervous system

Publisher: Elsevier BV

Date: 2016

DOI: 10.1016/J.BIOMATERIALS.2015.10.001

Abstract: Following neurotrauma, oxidative stress is spread via the astrocytic syncytium and is associated with increased aquaporin 4 (AQP4), inflammatory cell infiltration, loss of neurons and glia and functional deficits. Herein we evaluate multimodal polymeric nanoparticles functionalized with an antibody to an extracellular epitope of AQP4, for targeted delivery of an anti-oxidant as a therapeutic strategy following partial optic nerve transection. Using fluorescence microscopy, spectrophotometry, correlative nanoscale secondary ion mass spectrometry (NanoSIMS) and transmission electron microscopy, in vitro and in vivo, we demonstrate that functionalized nanoparticles are coated with serum proteins such as albumin and enter both macrophages and astrocytes when administered to the site of a partial optic nerve transection in rat. Antibody functionalized nanoparticles synthesized to deliver the antioxidant resveratrol are effective in reducing oxidative damage to DNA, AQP4 immunoreactivity and preserving visual function. Non-functionalized nanoparticles evade macrophages more effectively and are found more diffusely, including in astrocytes, however they do not preserve the optic nerve from oxidative damage or functional loss following injury. Our study highlights the need to comprehensively investigate nanoparticle location, interactions and effects, both in vitro and in vivo, in order to fully understand functional outcomes.

Extent of retinal ganglion cell death in the frog Litoria moorei after optic nerve regeneration induced by lesions of different sizes

Publisher: Wiley

Date: 22-03-2002

DOI: 10.1002/CNE.10213

Abstract: Some hibian retinal ganglion cells die during optic nerve regeneration. Here we have investigated whether ganglion cell death in the frog Litoria moorei is associated with the lesion site. For one experimental series, the optic nerve lesion extended for 0.15 mm in the other, it extended for 1.5 mm. The extent of ganglion cell death was estimated from cresyl violet-stained whole mounts at 24 weeks post lesion. In other animals, in idual regenerating axons were visualised in the optic nerve by horseradish peroxidase (HRP) labelling from 1 day to 24 weeks post lesion counterstaining with cresyl violet allowed examination of cells that repopulated the lesion site. Ganglion cell numbers fell significantly more after an extensive than after a localised lesion, long-term losses being 50% and 34%, respectively (P < 0.05). Regenerating axons were delayed in their passage across the cell-poor extensive lesion compared with the relatively cell-rich localised lesion. The differing rates of regeneration between series were matched by greater delay after extensive lesion in the return of visually guided behaviour as assessed by optokinetic horizontal head nystagmus. We suggest that delays in regeneration after an extensive lesion exacerbate ganglion cell death, indicating that conditions within the lesion are associated with the death of some ganglion cells.

Secondary Retinal Ganglion Cell Death and the Neuroprotective Effects of the Calcium Channel Blocker Lomerizine

Publisher: Association for Research in Vision and Ophthalmology (ARVO)

Date: 11-2009

DOI: 10.1167/IOVS.09-3717

Abstract: After partial optic nerve (ON) injury, intact retinal ganglion cells (RGCs) undergo secondary death, but the topographic distribution of this death is unknown, and it is unclear which cell death pathways are involved. Although the calcium channel blocker lomerizine reduces RGC death after partial ON injury, it is unknown whether this drug alleviates necrotic or apoptotic death. The dorsal ON was transected in adult Piebald-Virol-Glaxo (PVG) rats, and the site of secondary RGC death was determined using anterograde and retrograde DiI tracing. RGC death was assessed at 2 and 3 weeks. Retrograde tracing with fluorogold injected into the superior colliculus 3 days before euthanatization was used to identify RGCs undergoing secondary death. Overall cell loss was quantified using betaIII-tubulin immunohistochemistry. Lomerizine (30 mg/kg, oral) or vehicle was given twice daily, and retinal wholemounts were analyzed for necrotic morphology (nucleic acid stain) or anticleaved caspase-3 expression at 2 and 3 weeks. Ventral retina was identified as the site of secondary RGC death, and central and dorsal retinae were defined as sites of both primary and secondary death. Overall RGC loss occurred by 2 weeks in central and ventral retina (P < 0.05) and by 3 weeks in dorsal retina (P < 0.05). Secondary RGC death was characterized mainly by necrotic morphology, with caspase-3 expression in some RGCs. Lomerizine reduced secondary necrosis at 2 weeks and secondary caspase-3 expression at 3 weeks. Lomerizine had differential effects on necrotic and apoptotic death with time, but its inability to completely prevent secondary death suggests that full neuroprotection will require combinatorial treatments.

Effect of corticosteroids on brain growth in fetal sheep

Publisher: Ovid Technologies (Wolters Kluwer Health)

Date: 08-1999

DOI: 10.1016/S0029-7844(99)00265-3

Abstract: To compare the effects of single and repeated courses of corticosteroids on brain growth in fetal sheep. Pregnant sheep were given intramuscular betamethasone (0.5 mg/kg) at 104 days' gestation followed at 111, 118, and 124 days by equivalent volumes of sterile normal saline (n = 12) or betamethasone (n = 12). Controls received equivalent volumes of sterile normal saline at all four intervals (n = 12). Lambs were delivered at 125 (preterm) or 145 (term) days. After perfusion, we measured weights (grams) for whole brain, cerebrum, cerebellum, and brain stem, volumes (milliliters) for whole brain and cerebrum, and maximum cerebral anterior-posterior length, width, and depth (centimeters). In the single-injection group at preterm, there were no significant differences (P = .070) in whole-brain weight between the corticosteroid-treated animals (38.0 +/- 1.81 g) and controls (42.5 +/- 1.65 g). Cerebral length and depth were significantly reduced in the corticosteroid group (P < .05) other measures were not significantly different. At term, whole-brain weight was significantly lower (47.5 +/- 1.70 g P = .022) compared with controls (53.4 +/- 1.73 g). All other measures were significantly reduced (P < .05) except cerebral and brain-stem weights and cerebral length. In the group that received repeated injections at preterm, whole-brain weight was significantly reduced (35.5 +/- 1.65 g P = .005) compared with controls (42.5 +/- 1.65 g). All other measures were significantly reduced (P < .05) except cerebellar and brain-stem weights. At term, whole-brain weight was also significantly reduced (42.4 +/- 1.52 g P = .001) compared with controls (53.4 +/- 1.73 g) as were all other measures (P < .05). Administration of single and repeated courses of corticosteroids to pregnant sheep retarded fetal brain growth.

Barriers and facilitators to optimising inpatient bladder management after spinal cord injury

Publisher: Springer Science and Business Media LLC

Date: 26-05-2020

DOI: 10.1038/S41393-020-0487-6

EphA/ephrin-A interactions during optic nerve regeneration: restoration of topography and regulation of ephrin-A2 expression

Publisher: Elsevier BV

Date: 2004

DOI: 10.1016/J.MCN.2003.09.010

Mechanical stimulation of paralyzed vibrissal muscles following facial nerve injury in adult rat promotes full recovery of whisking

Publisher: Elsevier BV

Date: 04-2007

DOI: 10.1016/J.NBD.2006.12.016

Abstract: Many patients suffer lifelong disabilities after peripheral nerve injury. Insufficient recovery has been attributed to excessive axonal branching, axonal regrowth to improper targets and polyneuronal reinnervation of motor endplates. We used the rat facial nerve transection/suture model to quantify the effects of mechanical stimulation on the paralyzed whisker musculature. "Manual" stimulation involved briskly stroking the whiskers by hand in a manner that specifically mimicked normal whisker movement. "Environmental" stimulation involved enhanced whisker use as rats encountered objects in an enriched environment. Manual and environmental stimulation were also combined. Video-based motion analysis of vibrissal motor performance showed that daily manual, but not environmental, stimulation for 2 months resulted in full recovery of whisking. Polyneuronal reinnervation of motor endplates was reduced but not misdirected axonal regrowth. Our findings indicate the potential of use-specific training to enhance appropriate functional outcome after peripheral nerve injury and may be useful in a clinical rehabilitation setting.

A Preclinical Study of Standard Versus Accelerated Transcranial Magnetic Stimulation for Depression in Adolescents

Publisher: Mary Ann Liebert Inc

Date: 04-2022

DOI: 10.1089/CAP.2021.0100

Composite fluorescent vesicles based on ionic and cationic amphiphilic calix[4]arenes

Publisher: Royal Society of Chemistry (RSC)

Date: 2012

DOI: 10.1039/C2RA20491F

Barriers to Physical Activity in Individuals with Spinal Cord Injury: A Western Australian Study

Publisher: Cambridge University Press (CUP)

Date: 12-2011

DOI: 10.1375/JRC.17.2.74

Abstract: This study examined barriers to physical activity reported in iduals with spinal cord injury (SCI) and the degree to which these barriers differed across varying degrees of independence. Participants were 65 in iduals recruited from the Western Australian Spinal Cord Injury database. Data on physical activity participation and perceived barriers to physical activity participation were collected using a cross-sectional survey and analysed using independent s les t-tests. We found that, regardless of level of ambulation or ability to transfer, few participants reported being physically active. While there were no significant differences in the amount of barriers reported by in iduals with different levels of independence, the type of barriers reported varied across groups.

Transcranial pulsed magnetic field stimulation facilitates reorganization of abnormal neural circuits and corrects behavioral deficits without disrupting normal connectivity

Publisher: Wiley

Date: 05-01-2012

DOI: 10.1096/FJ.11-194878

Abstract: Although the organization of neuronal circuitry is shaped by activity patterns, the capacity to modify and/or optimize the structure and function of whole projection pathways using external stimuli is poorly defined. We investigate whether neuronal activity induced by pulsed magnetic fields (PMFs) alters brain structure and function. We delivered low-intensity PMFs to the posterior cranium of awake, unrestrained mice (wild-type and ephrin-A2A5(-/-)) that have disorganized retinocollicular circuitry and associated visuomotor deficits. Control groups of each genotype received sham stimulation. Following daily stimulation for 14 d, we measured biochemical, structural (anterograde tracing), and functional (electrophysiology and behavior) changes in the retinocollicular projection. PMFs induced BDNF, GABA, and nNOS expression in the superior colliculus and retina of wild-type and ephrin-A2A5(-/-) mice. Furthermore, in ephrin-A2A5(-/-) mice, PMFs corrected abnormal neuronal responses and selectively removed inaccurate ectopic axon terminals to improve structural and functional organization of their retinocollicular projection and restore normal visual tracking behavior. In contrast, PMFs did not alter the structure or function of the normal projection in wild-type mice. Sham PMF stimulation had no effect on any mice. Thus, PMF-induced biochemical changes are congruent with its capacity to facilitate beneficial reorganization of abnormal neural circuits without disrupting normal connectivity and function.

Bone marrow-derived mesenchymal stem cell transplantation does not improve quality of muscle reinnervation or recovery of motor function after facial nerve transection in rats

Publisher: Walter de Gruyter GmbH

Date: 06-06-2008

DOI: 10.1515/BC.2008.100

Abstract: Recently, we devised and validated a novel strategy in rats to improve the outcome of facial nerve reconstruction by daily manual stimulation of the target muscles. The treatment resulted in full recovery of facial movements (whisking), which was achieved by reducing the proportion of pathologically polyinnervated motor endplates. Here, we posed whether manual stimulation could also be beneficial after a surgical procedure potentially useful for treatment of large peripheral nerve defects, i.e., entubulation of the transected facial nerve in a conduit filled with suspension of isogeneic bone marrow-derived mesenchymal stem cells (BM-MSCs) in collagen. Compared to control treatment with collagen only, entubulation with BM-MSCs failed to decrease the extent of collateral axonal branching at the lesion site and did not improve functional recovery. Post-operative manual stimulation of vibrissal muscles also failed to promote a better recovery following entubulation with BM-MSCs. We suggest that BM-MSCs promote excessive trophic support for regenerating axons which, in turn, results in excessive collateral branching at the lesion site and extensive polyinnervation of the motor endplates. Furthermore, such deleterious effects cannot be overridden by manual stimulation. We conclude that entubulation with BM-MSCs is not beneficial for facial nerve repair.

Early decompression following cervical spinal cord injury: Examining the process of care from accident scene to surgery

Publisher: Mary Ann Liebert Inc

Date: 15-06-2016

DOI: 10.1089/NEU.2015.4207

Abstract: Early decompression may improve neurological outcome after spinal cord injury (SCI), but is often difficult to achieve because of logistical issues. The aims of this study were to 1) determine the time to decompression in cases of isolated cervical SCI in Australia and New Zealand and 2) determine where substantial delays occur as patients move from the accident scene to surgery. Data were extracted from medical records of patients aged 15-70 years with C3-T1 traumatic SCI between 2010 and 2013. A total of 192 patients were included. The median time from accident scene to decompression was 21 h, with the fastest times associated with closed reduction (6 h). A significant decrease in the time to decompression occurred from 2010 (31 h) to 2013 (19 h, p = 0.008). Patients undergoing direct surgical hospital admission had a significantly lower time to decompression, compared with patients undergoing pre-surgical hospital admission (12 h vs. 26 h, p < 0.0001). Medical stabilization and radiological investigation appeared not to influence the timing of surgery. The time taken to organize the operating theater following surgical hospital admission was a further factor delaying decompression (12.5 h). There was a relationship between the timing of decompression and the proportion of patients demonstrating substantial recovery (2-3 American Spinal Injury Association Impairment Scale grades). In conclusion, the time of cervical spine decompression markedly improved over the study period. Neurological recovery appeared to be promoted by rapid decompression. Direct surgical hospital admission, rapid organization of theater, and where possible, use of closed reduction, are likely to be effective strategies to reduce the time to decompression.

Erythropoietin is both neuroprotective and neuroregenerative following optic nerve transection

Publisher: Elsevier BV

Date: 05-2007

DOI: 10.1016/J.EXPNEUROL.2007.01.017

Abstract: The cytokine hormone erythropoietin (EPO) is neuroprotective in models of brain injury and disease, and protects retinal ganglion cells (RGC) from cell death after axotomy. Here, we assessed EPO's neuroprotective properties in vivo by examining RGC survival and axon regeneration at 4 weeks following intraorbital optic nerve transection in adult rat. EPO was administered as a single intravitreal injection at the time of transection (5, 10, 25, 50 units, PBS control). Intravitreal EPO (5, 10 units) significantly increased RGC somata and axon survival between the eye and transection site. Twenty five units did not improve survival of RGC somata but did increase axon survival between the eye and transection site. In addition, a small proportion of axons penetrated the transection site and regenerated up to 1 mm into the distal nerve. In a second series, intravitreal EPO (25 units) doubled the number of RGC axons regenerating along a length of peripheral nerve grafted onto the retrobulbar optic nerve. Our in vivo evidence of both neuroregeneration and neuroprotection, taken together with the natural occurrence of EPO within the body and its ability to cross the blood-brain barrier, suggests that it offers promise as a therapeutic agent for central nerve repair.

The Protein Corona of PEGylated PGMA-Based Nanoparticles is Preferentially Enriched with Specific Serum Proteins of Varied Biological Function

Publisher: American Chemical Society (ACS)

Date: 30-10-2017

DOI: 10.1021/ACS.LANGMUIR.7B02568

Abstract: The composition of the protein corona formed on poly(ethylene glycol)-functionalized (PEGylated) poly(glycidyl methacrylate) (PGMA) nanoparticles (NPs) was qualitatively and quantitatively compared to the protein corona on non-PEGylated PGMA NPs. Despite the reputation of PEGylated NPs for stealth functionality, we demonstrate the preferential enrichment of specific serum proteins of varied biological function in the protein corona on PEGylated NPs when compared to non-PEGylated NPs. Additionally, we suggest that the base material of polymeric NPs plays a role in the preferential enrichment of select serum proteins to the hard corona.

Changes to mitochondrial ultrastructure in optic nerve vulnerable to secondary degeneration in vivo are limited by irradiation at 670 nm

Publisher: Springer Science and Business Media LLC

Date: 08-09-2013

DOI: 10.1186/1471-2202-14-98

Abstract: Traumatic injury to the central nervous system results in damage to tissue beyond the primary injury, termed secondary degeneration. Key events thought to be associated with secondary degeneration involve aspects of mitochondrial function which may be modulated by red/near-infrared irradiation therapy (R/NIR-IT), but precisely how mitochondria are affected in vivo has not been investigated. Secondary degeneration was modelled by transecting the dorsal aspect of the optic nerve in adult rats and mitochondrial ultrastructure in intact ventral optic nerve vulnerable to secondary degeneration investigated with transmission electron microscopy. Despite reported increases in fission following central nervous system injury, we saw no change in mitochondrial densities in optic nerve vulnerable to secondary degeneration in vivo . However, in axons, frequency distributions of mitochondrial profile areas showed higher cumulative probabilities of smaller mitochondrial profiles at day 1 after injury. Glial mitochondrial profiles did not exhibit changes in area, but a more elliptical mitochondrial shape was observed at both day 1 and 7 following injury. Importantly, mitochondrial autophagic profiles were observed at days 1 and 7 in optic nerve vulnerable to secondary degeneration in vivo . Citrate synthase activity was used as an additional measure of mitochondrial mass in ventral optic nerve and was decreased at day 7, whereas mitochondrial aconitase activity increased at day 1 and day 28 after injury in optic nerve vulnerable to secondary degeneration. R/NIR-IT has been used to treat the injured central nervous system, with reported improvements in oxidative metabolism suggesting mitochondrial involvement, but ultrastructural information is lacking. Here we show that R/NIR-IT of injured animals resulted in distributions of mitochondrial areas and shape not significantly different from control and significantly reduced mitochondrial autophagic profiles. R/NIR-IT also resulted in decreased citrate synthase activity (day 7) and increased aconitase activity (day 1) in optic nerve vulnerable to secondary degeneration. These findings suggest that mitochondrial structure and activity of enzymes of the citric acid cycle are dynamically altered during secondary degeneration in vivo and R/NIR-IT may protect mitochondrial structure.

The influence of NaYF₄:Yb,Er size/phase on the multimodality of co-encapsulated magnetic photon-upconverting polymeric nanoparticles

Publisher: Royal Society of Chemistry (RSC)

Date: 2014

DOI: 10.1039/C4DT01597E

Abstract: Assessment of polymeric nanoparticles incorporating NaYF 4 :Yb,Er and Fe 3 O 4 as multimodal imaging probes in vitro .

The effect of myelotomy following low thoracic spinal cord compression injury in rats

Publisher: Elsevier BV

Date: 08-2018

DOI: 10.1016/J.EXPNEUROL.2018.04.011

Abstract: Myelotomy is a surgical procedure allowing removal of extravasated blood and necrotic tissue that is thought to attenuate secondary injury as well as promote recovery in experimental spinal cord injury (SCI) models and humans. Here we examined in rat whether myelotomy at 48 h after low-thoracic compressive SCI provided any benefit over a 12 week period. Compared to animals receiving SCI alone, myelotomy worsened BBB scores (p < 0.05) and also did not improve plantar stepping, ladder climbing, urinary bladder voiding or sensory function (thermal latency) during the 12-week period. Quantitative analyses of tissue sections at 12 weeks showed that myelotomy also did not reduce lesion volume nor alter immunohistochemical markers of axons in spared white matter bridges, microglia, astrocytes or serotinergic fibres. However, myelotomy reduced synaptophysin expression, a marker of synaptic plasticity. We conclude that further studies are required to evaluate myelotomy after SCI. (142 words).

Genesis of the frog retinal pigment epithelium

Publisher: Elsevier BV

Date: 10-1996

DOI: 10.1016/0165-3806(96)00125-3

Abstract: To examine cell generation in the frog retinal pigment epithelium (RPE), representative developmental stages from tail-bud to adulthood received a single injection of [3H]thymidine. Animals were killed either 24 h or several weeks later eyes were sectioned and processed by standard autoradiographic procedures and viewed by epi-polarised illumination. The distribution of [3H]thymidine-labelled cells indicated that the RPE is formed throughout life, including in adulthood, by cell addition at the ciliary margin, matching the pattern for the neural retina. In addition, a very small number of peripapillary RPE cells underwent ision but only in the adult.

FGF-2 is required to prevent astrogliosis in the facial nucleus after facial nerve injury and mechanical stimulation of denervated vibrissal muscles

Publisher: Journal of Biomedical Research

Date: 2016

DOI: 10.7555/JBR.30.20140042

Functional Topography and Integration of the Contralateral and Ipsilateral Retinocollicular Projections ofEphrin-A^−/−Mice

Publisher: Society for Neuroscience

Date: 16-07-2008

DOI: 10.1523/JNEUROSCI.1135-08.2008

Abstract: Topographically ordered projections are established by molecular guidance cues and refined by neuronal activity. Retinal input to a primary visual center, the superior colliculus (SC), is bilateral with a dense contralateral projection and a sparse ipsilateral one. Both projections are topographically organized, but in opposing anterior–posterior orientations. This arrangement provides functionally coherent input to each colliculus from the binocular visual field, supporting visual function. When guidance cues involved in contralateral topography (ephrin-As) are absent, crossed retinal ganglion cell (RGC) axons form inappropriate terminations within the SC. However, the organization of the ipsilateral projection relative to the abnormal contralateral input remains unknown, as does the functional capacity of both projections. We show here that in ephrin-A −/− mice, the SC contains an expanded, diffuse ipsilateral projection. Electrophysiological recording demonstrated that topography of visually evoked responses recorded from the contralateral superior colliculus of ephrin-A −/− mice displayed similar functional disorder in all genotypes, contrasting with their different degrees of anatomical disorder. In contrast, ipsilateral responses were retinotopic in ephrin-A2 −/− but disorganized in ephrin-A2/A5 −/− mice. The lack of integration of binocular input resulted in specific visual deficits, which could be reversed by occlusion of one eye. The discrepancy between anatomical and functional topography in both the ipsilateral and contralateral projections implies suppression of inappropriately located terminals. Moreover, the misalignment of ipsilateral and contralateral visual information in ephrin-A2/A5 −/− mice suggests a role for ephrin-As in integrating convergent visual inputs.

Neutralizing BDNF and FGF2 injection into denervated skeletal muscle improve recovery after nerve repair

Publisher: Wiley

Date: 18-06-2020

DOI: 10.1002/MUS.26991

Repeated prenatal corticosteroid administration delays astrocyte and capillary tight junction maturation in fetal sheep

Publisher: Wiley

Date: 17-07-2001

DOI: 10.1016/S0736-5748(01)00035-1

Abstract: Glucocorticoids are powerful regulators of cell differentiation and maturation. Their synthetic counterparts, the corticosteroids, are used widely in obstetric practice to enhance fetal lung maturation in cases of threatened preterm birth. Here we examined the effects of repeated corticosteroid administration on astrocyte and capillary tight junction development in the fetal sheep brain, selecting the corpus callosum for analysis. Pregnant ewes were given saline or betamethasone (0.5 mg/kg) at 104, 111, 118 and 124 days gestation. Lambs were delivered at term, terminally anaesthetized and transcardially perfused. Transverse semi-thin sections of the corpus callosum were cut and immuno-stained with antibody against glial fibrillary acidic protein (GFAP). Ultra-thin sections were examined in the electron microscope. The percentage area of GFAP staining was reduced in the corticosteroid-treated group compared to control (5.2 vs. 8.7%, P<0.05). The expression of GFAP in peri-capillary and parenchymal astrocytes was also reduced compared to control (peri-capillary: 3.0 vs. 9.5 microm2 parenchymal: 14.6 vs. 29.4 microm2, P<0.05). Furthermore, capillary tight junction maturation was delayed compared to control. Immature 'type II' junctions were more common in the corticosteroid-treated group (63 vs. 22%, P<0.05), whereas more mature 'type III' junctions were less common (27 vs. 65%, P<0.05). Our data suggest that repeated corticosteroids delay both astrocyte and capillary tight junction maturation. The implications for clinical practice are as yet unknown.

Evaluating the effects of nacre on human skin and scar cells in culture

Publisher: Oxford University Press (OUP)

Date: 2014

DOI: 10.1039/C4TX00004H

Multifunctional nanoadditives for the thermodynamic and kinetic stabilization of enzymes

Publisher: Royal Society of Chemistry (RSC)

Date: 2011

DOI: 10.1039/C1NR10786K

Abstract: Stabilization of enzymes has become a major focus in the quest to improve the activity, sustainability and recyclability of enzymes for their successful integration into both industry and medicine. Here, we describe the kinetic and thermodynamic stabilization of a variety of enzymes in the presence of cationic multifunctional polymeric nanoparticles.

Early intensive hand rehabilitation is not more effective than usual care plus one-to-one hand therapy in people with sub-acute spinal cord injury ('Hands On'): A randomised trial

Publisher: Elsevier BV

Date: 04-2016

DOI: 10.1016/J.JPHYS.2016.02.013

Abstract: What is the effect of adding an intensive task-specific hand-training program involving functional electrical stimulation to a combination of usual care plus three 15-minute sessions per week of one-to-one hand therapy in people with sub-acute tetraplegia? A parallel group, randomised, controlled trial. Participants were randomly assigned (1:1) via a computer-generated concealed block randomisation procedure to either a control or experimental intervention. Seventy people with C2 to T1 motor complete or incomplete tetraplegia within 6 months of injury. Participants were recruited from seven spinal units in Australia and New Zealand. Experimental participants received intensive training for one hand. Intensive training consisted of training with an instrumented exercise workstation in conjunction with functional electrical stimulation for 1 hour per day, 5 days per week for 8 weeks. Both groups received usual care and 15 minutes of one-to-one hand therapy three times per week without functional electrical stimulation. The primary outcome was the modified Action Research Arm Test reflecting arm and hand function, which was assessed at the end of the intervention, that is, 11 weeks after randomisation. Secondary outcomes were measured at 11 and 26 weeks. Sixty-six (94%) participants completed the post-intervention assessment and were included in the primary intention-to-treat analysis. The mean modified Action Research Arm Test score for experimental and control participants at the post-intervention assessment was 36.5 points (SD 16.0) and 33.2 points (SD 17.5), respectively, with an adjusted mean between-group difference of 0.9 points (95% CI -4.1 to 5.9). Adding an intensive task-specific hand-training program involving functional electrical stimulation to a combination of usual care plus three 15-minute sessions per week of one-to-one hand therapy does not improve hand function in people with sub-acute tetraplegia. Australian and New Zealand Trial Registry ACTRN12609000695202 and ClinicalTrials.gov NCT01086930.

rAAV.sFlt-1 Gene Therapy Achieves Lasting Reversal of Retinal Neovascularization in the Absence of a Strong Immune Response to the Viral Vector

Publisher: Association for Research in Vision and Ophthalmology (ARVO)

Date: 09-2009

DOI: 10.1167/IOVS.08-3253

Abstract: To determine the efficacy of rAAV.sFlt-1-mediated gene therapy in a transgenic mouse model of retinal neovascularization (trVEGF029) and to assess whether rAAV.sFlt-1 administration generated any deleterious, long-lasting immune response that could affect efficacy. trVEGF029 mice were injected subretinally with rAAV.sFlt-1 or phosphate-buffered saline. Fluorescein angiography and electroretinography were used to compare the extent of fluorescein leakage from retinal vessels and retinal function, respectively. A group of eyes was enucleated, and the retinal vasculature and morphology were studied by confocal and light microscopy. Cells were isolated from the posterior eyecups and spleens of a further group, and immune cell subset populations were investigated by flow cytometry. sFlt-1 protein levels in the eyes were evaluated by ELISA. After a single rAAV.sFlt-1 injection, sFlt-1 protein levels were upregulated, and there was a reduction in fluorescein leakage from the retinal vessels and an improvement in retinal function. Confocal microscopy of isolectin-IB4-labeled retinal wholemounts showed more normal-appearing capillary beds in rAAV.sFlt-1-injected than in PBS-injected trVEGF029 mouse eyes. Light microscopy demonstrated retinal morphology preservation, with fewer aberrant vessels invading the outer nuclear layer of rAAV.sFlt-1-injected eyes. Furthermore, the immune response to subretinal injection of rAAV.sFlt-1 was limited to a transient increase in CD45(+) leukocytes that disappeared by 4 weeks after injection. This transient increase was localized to the eye and did not affect long-term therapeutic efficacy. The data support the notion that rAAV.sFlt-1 gene therapy is safe and effective for the long-term inhibition of deleterious blood vessel growth in the eye.

The Minderoo-Monaco Commission on Plastics and Human Health

Publisher: Ubiquity Press, Ltd.

Date: 2023

DOI: 10.5334/AOGH.4056

Eliminating plastic pollution

Publisher: Frontiers Media SA

Date: 25-09-2019

DOI: 10.3389/FMARS.2019.00627

Correction: The Minderoo-Monaco Commission on Plastics and Human Health

Publisher: Ubiquity Press, Ltd.

Date: 2023

DOI: 10.5334/AOGH.4331

Maternally Administered Sustained-Release Naltrexone in Rats Affects Offspring Neurochemistry and Behaviour in Adulthood

Publisher: Public Library of Science (PLoS)

Date: 26-12-2012

DOI: 10.1371/JOURNAL.PONE.0052812

Whole-Body Vibration Improves Functional Recovery in Spinal Cord Injured Rats

Publisher: Mary Ann Liebert Inc

Date: 15-03-2013

DOI: 10.1089/NEU.2012.2653

Abstract: Whole-body vibration (WBV) is a relatively novel form of exercise used to improve neuromuscular performance in healthy in iduals. Its usefulness as a therapy for patients with neurological disorders, in particular spinal cord injury (SCI), has received little attention in clinical settings and, surprisingly, even less in animal SCI models. We performed severe compression SCI at a low-thoracic level in Wistar rats followed by daily WBV starting 7 (10 rats) or 14 (10 rats) days after injury (WBV7 and WBV14, respectively) and continued over a 12-week post-injury period. Rats with SCI but no WBV training (sham, 10 rats) and intact animals (10 rats) served as controls. Compared to sham-treated rats, WBV did not improve BBB score, plantar stepping, or ladder stepping during the 12-week period. Accordingly, WBV did not significantly alter plantar H-reflex, lesion volume, serotonergic input to the lumbar spinal cord, nor cholinergic or glutamatergic inputs to lumbar motoneurons at 12 weeks after SCI. However, compared to sham, WBV14, but not WBV7, significantly improved body weight support (rump-height index) during overground locomotion and overall recovery between 6-12 weeks and also restored the density of synaptic terminals in the lumbar spinal cord at 12 weeks. Most remarkably, WBV14 led to a significant improvement of bladder function at 6-12 weeks after injury. These findings provide the first evidence for functional benefits of WBV in an animal SCI model and warrant further preclinical investigations to determine mechanisms underpinning this noninvasive, inexpensive, and easily delivered potential rehabilitation therapy for SCI.

Failure to form a stable topographic map during optic nerve regeneration: abnormal activity-dependent mechanisms

Publisher: Elsevier BV

Date: 12-2003

DOI: 10.1016/J.EXPNEUROL.2003.08.013

Cellular and molecular changes to cortical neurons following low intensity repetitive magnetic stimulation at different frequencies

Publisher: Elsevier BV

Date: 2015

DOI: 10.1016/J.BRS.2014.09.012

Abstract: Repetitive transcranial magnetic stimulation is increasingly used as a treatment for neurological dysfunction. Therapeutic effects have been reported for low intensity rTMS (LI-rTMS) although these remain poorly understood. Our study describes for the first time a systematic comparison of the cellular and molecular changes in neurons in vitro induced by low intensity magnetic stimulation at different frequencies. We applied 5 different low intensity repetitive magnetic stimulation (LI-rMS) protocols to neuron-enriched primary cortical cultures for 4 days and assessed survival, and morphological and biochemical change. We show pattern-specific effects of LI-rMS: simple frequency pulse trains (10 Hz and 100 Hz) impaired cell survival, while more complex stimulation patterns (theta-burst and a biomimetic frequency) did not. Moreover, only 1 Hz stimulation modified neuronal morphology, inhibiting neurite outgrowth. To understand mechanisms underlying these differential effects, we measured intracellular calcium concentration during LI-rMS and subsequent changes in gene expression. All LI-rMS frequencies increased intracellular calcium, but rather than influx from the extracellular milieu typical of depolarization, all frequencies induced calcium release from neuronal intracellular stores. Furthermore, we observed pattern-specific changes in expression of genes related to apoptosis and neurite outgrowth, consistent with our morphological data on cell survival and neurite branching. Thus, in addition to the known effects on cortical excitability and synaptic plasticity, our data demonstrate that LI-rMS can change the survival and structural complexity of neurons. These findings provide a cellular and molecular framework for understanding what low intensity magnetic stimulation may contribute to human rTMS outcomes.

Limited restoration of visual function after partial optic nerve injury; a time course study using the calcium channel blocker lomerizine

Publisher: Elsevier BV

Date: 03-2010

DOI: 10.1016/J.BRAINRESBULL.2009.11.004

Abstract: Secondary degeneration is a process encompassing damage adjacent to a primary injury, usually involving increased Ca(2+) influx into neurons and glia. Lomerizine dihydrochloride is a calcium channel blocker with relatively selective CNS effects, currently in clinical trials for glaucoma. We have recently demonstrated that, following partial transection of the optic nerve (ON), 1 month of lomerizine treatment protects retinal ganglion cells (RGCs), incompletely preserves visual function and also limits elements of secondary degeneration, including macrophage infiltration. However, under some circumstances macrophages have been shown to have different supportive effects on RGC protection and regeneration, casting doubt on the benefit of longer term therapies that reduce macrophage numbers. Here, we determined whether shorter treatment times (1 day or 1 week) result in improved effects on RGC survival and visual function, and whether benefits are maintained after cessation of treatment. We demonstrate that 1 month of lomerizine is the minimum period required to restore the fast reset phase of the optokinetic nystagmus and maintain it for a further 2 months after cessation of treatment (p>0.05, not different from normal). While 1 week of lomerizine treatment results in temporary recovery of numbers of fast reset phases, the recovery is not maintained after treatment cessation. Similarly, protection of RGC densities requires 1 month of lomerizine treatment, but protection is not maintained after treatment cessation. Importantly, none of the lomerizine treatment protocols resulted in full restoration of visual function, confirming the necessity of combining lomerizine with other treatment modalities.

Early urinary tract infection after spinal cord injury

Publisher: Springer Science and Business Media LLC

Date: 06-08-2020

DOI: 10.1038/S41393-019-0337-6

Abstract: Retrospective audit. Examine factors associated with urinary tract infection (UTI), UTI incidence and impact on hospital length of stay (LOS) in new, inpatient adult traumatic spinal cord injury (SCI). Western Australian Hospitals managing SCI patients. Data on UTIs, bladder management and LOS were obtained from hospital databases and medical records over 26 months. Adherence to staff-administered intermittent catheterisation (staff-IC) was determined from fluid balance charts. Across the cohort (n = 70) UTI rate was 1.1 starts/100 days UTI by multi-resistant organisms 0.1/100 days. Having ≥1 UTIs compared with none and longer duration of initial urethral indwelling catheterisation (IDC) were associated with longer LOS (p-values < 0.001). For patients with ≥1 UTIs (n = 43/70), longer duration of initial IDC was associated with shorter time to first UTI (1 standard deviation longer [SD, 45.0 days], hazard ratio (HR): 0.7, 95% confidence interval [CI] 0.5-1.0, p-value 0.044). In turn, shorter time to first UTI was associated with higher UTI rate (1 SD shorter [30.7 days], rate ratio (RR): 1.32, 95%CI 1.0-1.7, p-value 0.039). During staff-IC periods (n = 38/70), protocols were followed (85.7% ≤ 6 h apart, 96.1% 800 mL and interruptions requiring temporary IDC were associated with higher UTI rates the following week (odds ratios (ORs): 1.6, 95%CI 1.1-2.3, p-value 0.009 and 3.9, 95%CI 2.6-5.9, p-value < 0.001 respectively). Reducing initial IDC duration and limiting staff-IC volumes could be investigated to possibly reduce inpatient UTIs and LOS. None.

VEGF-induced choroidal damage in a murine model of retinal neovascularisation

Publisher: BMJ

Date: 06-2008

DOI: 10.1136/BJO.2007.130898

Abstract: Photoreceptor-specific upregulation of vascular endothelial growth factor (VEGF) in a transgenic mouse model (Kimba) of retinal neovascularisation induces retinal vascular damage which appears similar to that in diabetic retinopathy. Here we have determined whether the choroidal vasculature is also affected in Kimba. Kimba mice were assessed with fundus fluorescein angiography for mild, moderate or severe retinal vascular leakage prior to preparation of choroidal corrosion casts for quantitative analysis using scanning electron microscopy. VEGF was located immunohistochemically. Choroidal abnormalities included microaneurysms, constriction, shrinkage and dropout in the capillaries and tortuosity and loops in the arteries and veins which were similar to those observed in corrosion casts of the human choroid in diabetes. Similar to human diabetes, choroidal neovascularisation was not observed. The severity of choroidal damage correlated with the extent of retinal vascular leakage. In addition to the expected presence of VEGF in photoreceptors, VEGF was also detected in the pigment epithelium and choroid in the transgenic mice. We show that elevated retinal VEGF levels trigger pathophysiological changes in the choroid. We suggest that therapies to prevent vascular damage in diabetes must target both the retinal and choroidal vasculatures.

Short-term low intensity PMF does not improve functional or histological outcomes in a rat model of transient focal cerebral ischemia

Publisher: Elsevier BV

Date: 06-2012

DOI: 10.1016/J.BRAINRES.2012.04.006

Abstract: Stimulation with pulsed magnetic fields (PMF) is a non-invasive technique that can modulate neural activity and has the potential to facilitate functional recovery and tissue preservation/repair following brain injury. The effect of low intensity (8 mT) PMF on functional recovery and infarct tissue volume was assessed in a middle cerebral artery occlusion model of transient focal ischemia in Spontaneously Hypertensive rats. Rats received a combination of PMF protocols, including high and low frequencies and recovery was monitored over eight days. PMF treatment had no effect on functional recovery or infarct volume. Infarcted tissue accounted for ≈8% of total brain volume, encompassing both cortical and subcortical structures. The microglial and astrocytic response to PMF treatment was monitored and there was no change in glial scarring, however there was increased macrophage infiltration in animals that received chronic high (6-9 Hz) and low (1 Hz) stimulation. There was no effect of PMF on the degree of cell death observed within the ischemic core, with no TUNEL positive cells observed in the non-infarcted tissue. No detrimental side-effects of PMF were observed, indicating that low-intensity PMF may have limited safety concerns for future human and animal studies.

Regenerating optic axons restore topography after incomplete optic nerve injury

Publisher: Wiley

Date: 29-08-2007

DOI: 10.1002/CNE.21477

Abstract: Following complete optic nerve injury in a lizard, Ctenophorus ornatus, retinal ganglion cell (RGC) axons regenerate but fail to restore retinotectal topography unless animals are trained on a visual task (Beazley et al. [ 1997] J Comp Neurol 370:105-120, [2003] J Neurotrauma 20:1263-1270). Here we show that incomplete injury, which leaves some RGC axons intact, restores normal topography. Strict RGC axon topography allowed us to preserve RGC axons on one side of the nerve (projecting to medial tectum) while lesioning those on the other side (projecting to lateral tectum). Topography and response properties for both RGC axon populations were assessed electrophysiologically. The majority of intact RGC axons retained appropriate topography in medial tectum and had normal, consistently brisk, reliable responses. Regenerate RGC axons fell into two classes: those that projected topographically to lateral tectum with responses that tended to habituate and those that lacked topography, responded weakly, and habituated rapidly. Axon tracing by localized retinal application of carbocyanine dyes supported the electrophysiological data. RGC soma counts were normal in both intact and axotomized RGC populations, contrasting with the 30% RGC loss after complete injury. Unlike incomplete optic nerve injury in mammals, where RGC axon regeneration fails and secondary cell death removes many intact RGC somata, lizards experience a "win-win" situation: intact RGC axons favorably influence the functional outcome for regenerating ones and RGCs do not succumb to either primary or secondary cell death.

Early Proliferation Does Not Prevent the Loss of Oligodendrocyte Progenitor Cells during the Chronic Phase of Secondary Degeneration in a CNS White Matter Tract

Publisher: Public Library of Science (PLoS)

Date: 11-06-2013

DOI: 10.1371/JOURNAL.PONE.0065710

Manual stimulation of facial muscles improves functional recovery after hypoglossal-facial anastomosis and interpositional nerve grafting of the facial nerve in adult rats

Publisher: Elsevier BV

Date: 10-2007

DOI: 10.1016/J.NBD.2007.07.006

Abstract: The facial nerve in humans is often prone to injuries requiring surgical intervention. In the best case, nerve reconstruction is achieved by a facial-facial anastomosis (FFA), i.e. suture of the proximal and distal stumps of the severed facial nerve. Although a method of choice, FFA rarely leads to a satisfactory functional recovery. We have recently devised and validated, in an established experimental paradigm in rats, a novel strategy to improve the outcome of FFA by daily manual stimulation (MS) of facial muscles. This treatment results in full recovery of facial movements (whisking) and is achieved by reducing the proportion of functionally detrimental poly-innervated motor end-plates. Here we asked whether MS could also be beneficial after two other commonly used surgical methods of clinical facial nerve reconstruction namely hypoglossal-facial anastomosis (HFA) and interpositional nerve grafting (IPNG) which, however, seem to have a poorer outcome compared to FFA. Compared to FFA, daily MS for 2 months after HFA and IPGN did not completely restore function but, nevertheless, significantly improved the litude of whisker movements by 50% compared with untreated animals. Functional improvement was associated with a reduction in the proportion of polyinnervated end-plates. MS did not reduce the extent of axonal branching at the lesion site nor the subsequent misdirected axonal regrowth to inappropriate targets. Our data show that a simple approach leading to improved quality of muscle fiber reinnervation is functionally beneficial after different types of clinically relevant surgical interventions.

Near infrared light reduces oxidative stress and preserves function in CNS tissue vulnerable to secondary degeneration following partial transection of the optic nerve

Publisher: Mary Ann Liebert Inc

Date: 11-2010

DOI: 10.1089/NEU.2010.1426

Abstract: Traumatic injury to the central nervous system (CNS) is accompanied by the spreading damage of secondary degeneration, resulting in further loss of neurons and function. Partial transection of the optic nerve (ON) has been used as a model of secondary degeneration, in which axons of retinal ganglion cells in the ventral ON are spared from initial dorsal injury, but are vulnerable to secondary degeneration. We have recently demonstrated that early after partial ON injury, oxidative stress spreads through the ventral ON vulnerable to secondary degeneration via astrocytes, and persists in the nerve in aggregates of cellular debris. In this study, we show that diffuse transcranial irradiation of the injury site with far red to near infrared (NIR) light (WARP 10 LED array, center wavelength 670 nm, irradiance 252 W/m(-2), 30 min exposure), as opposed to perception of light at this wavelength, reduced oxidative stress in areas of the ON vulnerable to secondary degeneration following partial injury. The WARP 10 NIR light treatment also prevented increases in NG-2-immunopositive oligodendrocyte precursor cells (OPCs) that occurred in ventral ON as a result of partial ON transection. Importantly, normal visual function was restored by NIR light treatment with the WARP 10 LED array, as assessed using optokinetic nystagmus and the Y-maze pattern discrimination task. To our knowledge, this is the first demonstration that 670-nm NIR light can reduce oxidative stress and improve function in the CNS following traumatic injury in vivo.

Nanoparticle-mediated internalisation and release of a calcium channel blocker

Publisher: Royal Society of Chemistry (RSC)

Date: 2012

DOI: 10.1039/C2RA21058D

Chapter 23 Manual Stimulation of Target Muscles has Different Impact on Functional Recovery after Injury of Pure Motor or Mixed Nerves

Publisher: Elsevier

Date: 2009

DOI: 10.1016/S0074-7742(09)87023-2

Numbers of Axons in Spared Neural Tissue Bridges But Not Their Widths or Areas Correlate With Functional Recovery in Spinal Cord-Injured Rats

Publisher: Oxford University Press (OUP)

Date: 28-06-2020

DOI: 10.1093/JNEN/NLAA050

Abstract: The relationships between various parameters of tissue damage and subsequent functional recovery after spinal cord injury (SCI) are not well understood. Patients may regain micturition control and walking despite large postinjury medullar cavities. The objective of this study was to establish possible correlations between morphological findings and degree of functional recovery after spinal cord compression at vertebra Th8 in rats. Recovery of motor (Basso, Beattie, Bresnahan, foot-stepping angle, rump-height index, and ladder climbing), sensory (withdrawal latency), and bladder functions was analyzed at 1, 3, 6, 9, and 12 weeks post-SCI. Following perfusion fixation, spinal cord tissue encompassing the injury site was cut in longitudinal frontal sections. Lesion lengths, lesion volumes, and areas of perilesional neural tissue bridges were determined after staining with cresyl violet. The numbers of axons in these bridges were quantified after staining for class III β-tubulin. We found that it was not the area of the spared tissue bridges, which is routinely determined by magnetic resonance imaging (MRI), but the numbers of axons in them that correlated with functional recovery after SCI (Spearman’s ρ & 0.8 p & 0.001). We conclude that prognostic statements based only on MRI measurements should be considered with caution.

Chronic Swelling and Abnormal Myelination during Secondary Degeneration after Partial Injury to a Central Nervous System Tract

Publisher: Mary Ann Liebert Inc

Date: 06-2011

DOI: 10.1089/NEU.2010.1665

Abstract: Secondary degeneration is a serious consequence of traumatic injury to the central nervous system (CNS) and involves the progressive loss of neurons and function. However, while disruption to myelin has been observed in spared axons, the ultrastructural abnormalities that occur in myelin and axons spatially separated from the primary injury and susceptible exclusively to secondary degeneration are unknown. We used a model of secondary degeneration in which the dorsal aspect of rat optic nerve (ON) was transected leaving the central/ventral ON undamaged, but vulnerable to secondary degeneration. Transmission electron microscopy of the central/ventral ON at 1 and 3 months was used to quantify secondary changes in axon diameter, myelin sheath thickness and morphology, compared to normal animals. Three months after partial ON transection, cross-sectional nerve area at the injury site was increased (p ≤ 0.05), and changes in axons and myelin sheaths were detected in the central/ventral ON. Although myelin sheath thickness remained normal at both time points, average axon diameter significantly increased at 3 months. The density of the total axon population was decreased by 1 month, reflecting loss of retinal ganglion cells as previously published, with a decrease in the density of normally-myelinated axons, but an increase in unmyelinated axon density (p ≤ 0.05). Myelin basic protein immunoreactivity and fluoromyelin staining were also significantly reduced. Within four subpopulations of abnormally-myelinated axons, there was: no change in lightly-myelinated axons an increase in axons with excessive myelination (at 1 month) and an increase in the density of axons with partial and fully-decompacted myelin (at 3 months, p ≤ 0.05). Chronic axon swelling and myelin sheath compaction defects are features of secondary degeneration, and may contribute to the reported loss of ON function following partial transection.

Announcing the Minderoo – Monaco Commission on Plastics and Human Health

Publisher: Ubiquity Press, Ltd.

Date: 2022

DOI: 10.5334/AOGH.3916

Reply to Letter re: “Optimal Bladder Management Following Spinal Cord Injury: Evidence, Practice and a Cooperative Approach Driving Future Directions in Australia”

Publisher: Elsevier BV

Date: 09-2019

DOI: 10.1016/J.APMR.2019.05.021

University Of Western Australia

Location: Australia

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Queen Elizabeth College

Location: United Kingdom of Great Britain and Northern Ireland

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Minderoo Foundation

Location: Australia

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King’s College

Location: United Kingdom of Great Britain and Northern Ireland

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A Core Western Australian Cell Sorting Facility - Ultra-Small Objects And Rare Cell Populations

Start Date: 2009

End Date: 2009

Funder: Australian Research Council

A Cryopreparation Facility For Western Australia

Start Date: 2008

End Date: 2008

Funder: Australian Research Council

NETVISION: AUSTRALIA'S NATIONAL VISION RESEARCH NETWORK

Start Date: 2003

End Date: 2004

Funder: Australian Research Council

A Neural Network: Understanding Brain Function

Start Date: 2003

End Date: 2003

Funder: Australian Research Council

Use It Or Lose It: Training To Restore Vision After Optic Nerve Damage

Start Date: 2004

End Date: 2006

Funder: National Health and Medical Research Council

Harnessing Plasticity In The Brain To Improve Function And Repair

Start Date: 2010

End Date: 2012

Funder: National Health and Medical Research Council

In-Vivo Multispectral And X-ray Micro-CT Imaging: Founding A Western Australian Small Animal Imaging Core Facility

Start Date: 2010

End Date: 2010

Funder: Australian Research Council

Multiphoton Confocal Microscope For High-speed, Deep Tissue Imaging And Multimodal Nanoscale Characterisation

Start Date: 2011

End Date: 2011

Funder: Australian Research Council

Nuclear Magnetic Resonance Microimaging And Relaxometry Facility

Start Date: 2009

End Date: 2009

Funder: Australian Research Council

MALDI Imaging And Protein Analysis Facility For WA

Start Date: 2008

End Date: 2008

Funder: Australian Research Council

Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0454017

Start Date: 01-2004

End Date: 12-2004

Amount: $582,598.00

Funder: Australian Research Council

Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0882866

Start Date: 12-2008

End Date: 12-2009

Amount: $470,000.00

Funder: Australian Research Council

Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0668413

Start Date: 12-2006

End Date: 12-2007

Amount: $723,000.00

Funder: Australian Research Council

Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0560712

Start Date: 04-2005

End Date: 06-2005

Amount: $630,837.00

Funder: Australian Research Council

Discovery Projects - Grant ID: DP0988351

Start Date: 07-2009

End Date: 06-2014

Amount: $590,000.00

Funder: Australian Research Council

Linkage Projects - Grant ID: LP100100812

Start Date: 08-2010

End Date: 04-2015

Amount: $479,000.00

Funder: Australian Research Council

Linkage Projects - Grant ID: LP110100201

Start Date: 10-2011

End Date: 12-2014

Amount: $260,000.00

Funder: Australian Research Council

Special Research Initiatives - Grant ID: SR0354726

Start Date: 12-2003

End Date: 12-2004

Amount: $10,000.00

Funder: Australian Research Council

Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0989788

Start Date: 01-2009

End Date: 01-2010

Amount: $108,481.00

Funder: Australian Research Council

Linkage Infrastructure, Equipment And Facilities - Grant ID: LE110100146

Start Date: 2011

End Date: 12-2012

Amount: $500,000.00

Funder: Australian Research Council

Discovery Projects - Grant ID: DP1094217

Start Date: 2010

End Date: 06-2013

Amount: $495,000.00

Funder: Australian Research Council

Linkage Infrastructure, Equipment And Facilities - Grant ID: LE100100217

Start Date: 2010

End Date: 05-2011

Amount: $450,000.00

Funder: Australian Research Council

Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0882893

Start Date: 2008

End Date: 12-2008

Amount: $260,000.00

Funder: Australian Research Council

Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0989782

Start Date: 10-2009

End Date: 10-2010

Amount: $524,000.00

Funder: Australian Research Council

Special Research Initiatives - Grant ID: SR0354793

Start Date: 2004

End Date: 12-2004

Amount: $10,000.00

Funder: Australian Research Council