ORCID Profile
0000-0002-9797-5626
Current Organisations
Uppsala University Hospital
,
Upsala University
,
Lunds universitet Medicinska fakulteten
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Publisher: Elsevier BV
Date: 2005
DOI: 10.1016/J.NEUROSCIENCE.2005.04.048
Abstract: Traumatic brain injury causes long-term neurological motor and cognitive deficits, often with limited recovery. The inability of CNS axons to regenerate following traumatic brain injury may be due, in part, to inhibitory molecules associated with myelin. One of these myelin-associated proteins, Nogo-A, inhibits neurite outgrowth in vitro, and inhibition of Nogo-A in vivo enhances axonal outgrowth and sprouting and improves outcome following experimental CNS insults. However, the involvement of Nogo-A in the neurobehavioral deficits observed in experimental traumatic brain injury remains unknown and was evaluated in the present study using the 11C7 monoclonal antibody against Nogo-A. Anesthetized, male Sprague-Dawley rats were subjected to either lateral fluid percussion brain injury of moderate severity (2.5-2.6 atm) or sham injury. Beginning 24 h post-injury, monoclonal antibody 11C7 (n=17 injured, n=6 shams included) or control Ab (IgG) (n=16 injured, n=5 shams included) was infused at a rate of 5 microl/h over 14 days into the ipsilateral ventricle using osmotic minipumps connected to an implanted cannula. Rats were assessed up to 4 weeks post-injury using tests for neurological motor function (composite neuroscore, and sensorimotor test of adhesive paper removal) and, at 4 weeks, cognition was assessed using the Morris water maze. Hippoc al CA3 pyramidal neuron damage and corticospinal tract sprouting, using an anterograde tracer (biotinylated dextran amine), were also evaluated. Brain injury significantly increased sprouting from the uninjured corticospinal tract but treatment with monoclonal antibody 11C7 did not further increase the extent of sprouting nor did it alter the extent of CA3 cell damage. Animals treated with 11C7 showed no improvement in neurologic motor deficits but did show significantly improved cognitive function at 4 weeks post-injury when compared with brain-injured, IgG-treated animals. To our knowledge, the present findings are the first to suggest that (1) traumatic brain injury induces axonal sprouting in the corticospinal tract and this sprouting may be independent of myelin-associated inhibitory factors and (2) that post-traumatic inhibition of Nogo-A may promote cognitive recovery unrelated to sprouting in the corticospinal tract or neuroprotective effects on hippoc al cell loss following experimental traumatic brain injury.
Publisher: Cold Spring Harbor Laboratory
Date: 09-09-2022
DOI: 10.1101/2022.09.07.506982
Abstract: Traumatic brain injury (TBI) is a leading cause of chronic brain impairment and results in a robust, but poorly understood, neuroinflammatory response that contributes to the long-term pathology. We used snRNA-seq to study transcriptomic changes in different cell populations in human brain tissue obtained acutely after severe, life-threatening TBI. This revealed a unique transcriptional response in oligodendrocyte precursors and mature oligodendrocytes, including the activation of a robust innate immune response, indicating an important role for oligodendroglia in the initiation of neuroinflammation. The activation of an innate immune response correlated with transcriptional upregulation of endogenous retroviruses in oligodendroglia. This observation was causally linked in vitro using human glial progenitors, implicating these ancient viral sequences in human neuroinflammation. In summary, this work provides a unique insight into the initiating events of the neuroinflammatory response in TBI, which has new therapeutic implications.
Publisher: JMIR Publications Inc.
Date: 17-04-2023
DOI: 10.2196/37442
Abstract: Core outcome sets (COSs) are important and necessary as they help standardize reporting in research studies. Cranioplasty following traumatic brain injury (TBI) or stroke is becoming increasingly common, leading to an ever-growing clinical and research interest, especially regarding the optimal material, cost-effectiveness, and timing of cranioplasty concerning neurological recovery and complications. Consequently, heterogeneous reporting of outcomes from such erse studies has led to limited meta-analysis ability and an ongoing risk of outcome reporting bias. This study aims to define a standardized COS for reporting in all future TBI and stroke cranioplasty studies. This study has four aims: (1) undertake a systematic review to collate the most current outcome measures used within the cranioplasty literature (2) undertake a qualitative study to understand better the views of clinicians, patients' relatives, and allied health professionals regarding clinical outcomes following cranioplasty (3) undertake a Delphi survey as part of the process of gaining consensus for the COS and (4) finalize consensus through a consensus meeting resulting in the COS. An international steering committee has been formed to guide the development of the COS. In addition, recommendations from other clinical initiatives such as COMET (Core Outcomes and Effectiveness Trials) and OMERACT (Outcome Measures in Rheumatology) have been adhered to. Phase 1 is data collection through a systematic review and qualitative study. Phase 2 is the COS development through a Delphi survey and consensus meetings with consensus definitions decided and agreed upon before the Delphi survey begins to avoid bias. Phase 1 started at the end of 2019, following ethical approval in December 2019, and the project completion date is planned for the end of 2022 or beginning of 2023. This study should result in a consensus on a COS for cranioplasty, following TBI or stroke, to help standardize outcome reporting for future studies, which can be applied to future research and clinical services, help align future studies, build an increased understanding of cranioplasty and its impact on a patient’s function and recovery, and help standardize the evidence base. DERR1-10.2196/37442
Publisher: Springer Science and Business Media LLC
Date: 21-07-2015
Publisher: JMIR Publications Inc.
Date: 25-02-2022
Abstract: ore outcome sets (COSs) are important and necessary as they help standardize reporting in research studies. Cranioplasty following traumatic brain injury (TBI) or stroke is becoming increasingly common, leading to an ever-growing clinical and research interest, especially regarding the optimal material, cost-effectiveness, and timing of cranioplasty concerning neurological recovery and complications. Consequently, heterogeneous reporting of outcomes from such erse studies has led to limited meta-analysis ability and an ongoing risk of outcome reporting bias. This study aims to define a standardized COS for reporting in all future TBI and stroke cranioplasty studies. his study has four aims: (1) undertake a systematic review to collate the most current outcome measures used within the cranioplasty literature (2) undertake a qualitative study to understand better the views of clinicians, patients' relatives, and allied health professionals regarding clinical outcomes following cranioplasty (3) undertake a Delphi survey as part of the process of gaining consensus for the COS and (4) finalize consensus through a consensus meeting resulting in the COS. n international steering committee has been formed to guide the development of the COS. In addition, recommendations from other clinical initiatives such as COMET (Core Outcomes and Effectiveness Trials) and OMERACT (Outcome Measures in Rheumatology) have been adhered to. Phase 1 is data collection through a systematic review and qualitative study. Phase 2 is the COS development through a Delphi survey and consensus meetings with consensus definitions decided and agreed upon before the Delphi survey begins to avoid bias. hase 1 started at the end of 2019, following ethical approval in December 2019, and the project completion date is planned for the end of 2022 or beginning of 2023. his study should result in a consensus on a COS for cranioplasty, following TBI or stroke, to help standardize outcome reporting for future studies, which can be applied to future research and clinical services, help align future studies, build an increased understanding of cranioplasty and its impact on a patient’s function and recovery, and help standardize the evidence base. ERR1-10.2196/37442
No related grants have been discovered for Niklas Marklund.