ORCID Profile
0000-0003-0984-7665
Current Organisation
University of Calgary Faculty of Medicine
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Publisher: Society for Neuroscience
Date: 02-07-2008
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2007
DOI: 10.1161/STROKEAHA.106.476507
Abstract: Background and Purpose— Concomitant infection can exacerbate damage caused by cerebral ischemia. However, the interaction between and relative importance of the febrile and inflammatory components of the immune response is still unknown. Methods— Male Sprague-Dawley rats were subjected to a 2-vessel occlusion with hypotension, immediately followed by intraperitoneal injection of lipopolysaccharide or pyrogen-free saline. Results— Inflammation immediately after 2-vessel occlusion exacerbated hippoc al cell loss at 3 days and enhanced anxiety-related behaviors in the elevated plus maze and open field. These effects were not associated with differences in body temperature changes or with hippoc al pro-inflammatory cytokine production or hippoc al microglial activation. Conclusion— We show a previously undocumented dissociation between lipopolysaccharide-exacerbated damage after global ischemia in the rat and the temperature and acute brain immune response, indicating that the mechanism for enhanced lipopolysaccharide damage is hippoc al cytokine and temperature independent in this case.
Publisher: Elsevier BV
Date: 10-2005
DOI: 10.1016/J.TEM.2005.08.001
Abstract: A recent paper by Huber, Veinante and Stoop reports electrophysiological studies in slices of the amygdala in which the authors are able to demonstrate a cellular and spatial dissociation between the sites of action of oxytocin and vasopressin. These studies are important for determining how these brain peptides might gate autonomic responses to fear and other emotional stimuli.
Publisher: Wiley
Date: 04-2010
Publisher: American Physiological Society
Date: 2011
DOI: 10.1152/AJPENDO.00516.2010
Abstract: The early life environment can be crucial in influencing the development of an animal's long-term physiology. There is now much evidence to suggest that perinatal challenges to an animal's immune system will result in changes in adult rat behavior, physiology, and molecular pathways following a single inflammatory event during development caused by the bacterial endotoxin lipopolysaccharide (LPS). In particular, it is now apparent that neonatal LPS administration can influence the adult neuroimmune response to a second LPS challenge through hypothalamic-pituitary-adrenal axis modifications, some of which are caused by alterations in peripheral prostaglandin synthesis. These pronounced changes are accompanied by a variety of alterations in a number of disparate aspects of endocrine physiology, with significant implications for the health and well-being of the adult animal. In this review, we discuss the newly elucidated mechanisms by which neonatal immune challenge can permanently alter an animal's endocrine and metabolic physiology and the implications this has for various disease states.
Publisher: Springer Science and Business Media LLC
Date: 04-01-2006
Abstract: Many aspects of mammalian physiology are functionally immature at birth and continue to develop throughout at least the first few weeks of life. Animals are therefore vulnerable during this time to environmental influences such as stress and challenges to the immune system that may permanently affect adult function. The adult immune system is uniquely sensitive to immune challenges encountered during the neonatal period, but it is unknown where the critical window for this programming lies. We subjected male Sprague-Dawley rats at postnatal day (P)7, P14, P21, and P28 to either a saline or lipopolysaccharide (LPS) injection and examined them in adulthood for differences in responses to a further LPS injection. Adult febrile and cyclooxygenase-2 responses to LPS were attenuated in rats given LPS at P14 and P21, but not in those treated at P7 or P28, while P7-LPS rats displayed lower adult body weights than those treated at other times. P28-LPS rats also tended to display enhanced anxiety in the elevated plus maze. In further experiments, we examined maternal-pup interactions, looking at the mothers' preference in two pup-retrieval tasks, and found no differences in maternal attention to LPS-treated pups. We therefore demonstrate a 'critical window' for the effects of a neonatal immune challenge on adult febrile responses to inflammation and suggest that there are other critical time points during development for the programming of adult physiology. We also show that the neonatal LPS effects on the adult immune system are not likely due to overt differences in maternal attention.
Publisher: Elsevier BV
Date: 07-2006
DOI: 10.1016/J.BBI.2005.08.004
Abstract: Male and female rats display significant gender-associated differences in their responses to an immune challenge, and gender-specific alterations in many aspects of physiology are seen after a variety of interventions during the neonatal period. It is well-established that neonatal exposure to an immune challenge can alter centrally mediated inflammatory responses in adult male rats and yet little is known about female responses after a similar challenge. We therefore asked if neonatal exposure to lipopolysaccharide (LPS) would alter febrile and hypothalamic cyclooxygenase (COX)-2 responses to an adult immune challenge in female rats. Female Sprague-Dawley rats were administered a single injection of the bacterial endotoxin LPS at postnatal day 14 and were examined as adults for febrile, COX-2 and activity changes to LPS, as well as responses to interleukin (IL)-1beta. Adult female rat responses were similar to those we have seen previously for the males in that febrile and hypothalamic COX-2 responses to adult LPS were attenuated in neonatally LPS-treated animals. Responses to adult IL-1beta were unaffected. Interestingly, females did not display the elevated basal hypothalamic COX-2 that was previously seen in males. Thus we demonstrate that, like in the males, neonatal exposure to LPS has a powerful effect on adult responses to further LPS challenge in the female rats.
Publisher: American Physiological Society
Date: 08-2007
DOI: 10.1152/AJPREGU.00262.2007
Abstract: The perinatal environment plays a crucial role in programming many aspects of adult physiology. Myriad stressors during pregnancy, from maternal immune challenge to nutritional deficiency, can alter long-term body weight set points of the offspring. In light of the increasing concern over body weight issues, such as obesity and anorexia, in modern societies and accumulating evidence that developmental stressors have long-lasting effects on other aspects of physiology (e.g., fever, pain), we explored the role of immune system activation during neonatal development and its impact on body weight regulation in adulthood. Here we present a thorough evaluation of the effects of immune system activation (LPS, 100 μg/kg ip) at postnatal days 3, 7, or 14 on long-term body weight, adiposity, and body weight regulation after a further LPS injection (50 μg/kg ip) or fasting and basal and LPS-induced circulating levels of the appetite-regulating proinflammatory cytokine leptin. We show that neonatal exposure to LPS at various times during the neonatal period has no long-term effects on growth, body weight, or adiposity. We also observed no effects on body weight regulation in response to a short fasting period or a further exposure to LPS. Despite reductions in circulating leptin levels in response to LPS during the neonatal period, no long-term effects on leptin were seen. These results convincingly demonstrate that adult body weight and weight regulation are, unlike many other aspects of adult physiology, resistant to programming by a febrile-dose neonatal immune challenge.
Publisher: Elsevier BV
Date: 11-2005
DOI: 10.1016/J.BBR.2005.06.032
Abstract: Neonatal exposure to an immune challenge has been shown to alter many facets of adult physiology including fever responses to a similar infection. However, there is a paucity of information regarding its effects on adult behaviours. Male Sprague-Dawley rats were administered a single injection of the bacterial endotoxin lipopolysaccharide (LPS) at 14 days old and were compared, when they reached adulthood, with neonatally saline-treated controls in several behavioural tests of unconditioned fear and anxiety. There was no effect of the neonatal treatment on performance in either the elevated plus maze, modified Porsolt's forced swim test or the open field test. However, neonatally LPS-treated rats did show significantly reduced exploration of novel objects introduced to the open field arena, indicating an effect of the neonatal immune challenge on behaviours relating to anxiety in the adult.
Publisher: SAGE Publications
Date: 10-08-2005
Abstract: Infection, inflammation, and hyperthermia associated with cerebral ischaemia are known to contribute to enhanced neuronal cell loss and more severe behavioural deficits. Because neonatal exposure to an immune challenge has been shown to alter the severity of inflammatory and febrile responses to a further immune challenge experienced in adulthood, we hypothesised that this could also alter temperature responses and neuronal survival after ischaemia. Thus, male Sprague–Dawley rats were treated at postnatal day 14 with a single injection of the bacterial endotoxin lipopolysaccharide (LPS) and were examined as adults for temperature changes, behavioural deficits, and neuronal cell loss associated with global cerebral ischaemia after a two-vessel occlusion (2 VO). Neonatally LPS-treated rats showed behavioural differences in a novel object exploration paradigm, as well as altered temperature responses to the 2 VO compared with neonatally salinetreated controls. Interestingly, these neonatally LPS-treated rats also showed increased cell loss in the central nucleus of the amygdala, a region that is important in the processing of emotional responses, but that is not usually examined in animal models of cerebral ischaemia. No differences were seen in the CA1, CA3, or dentate gyrus regions of the hippoc us. This work shows the importance of examining brain regions other than the hippoc us in association with global ischaemia. We also highlight the importance of the early period of development in programming an animal's ability to deal with injury such as cerebral ischaemia in adulthood.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2005
DOI: 10.1016/J.PAIN.2005.09.022
Abstract: Intense pain or intense peripheral inflammation experienced during development can have pronounced effects upon adult pain sensation. However, little is known about the more commonly encountered mild systemic inflammation, such as that experienced with mild illness. Neonatal exposure to lipopolysaccharide (LPS), an established model of immune system activation, has been shown to affect febrile and cyclooxygenase-2 (COX-2) responses to a similar exposure in adulthood. Adult LPS also elicits a range of sickness behaviours, including enhanced responses to painful stimuli. We, therefore, hypothesized that adult sensation and pain responses could be affected by a neonatal LPS challenge. Male and female Sprague-Dawley rats were administered LPS at postnatal day 14 and were tested in adulthood for nociceptive responses to thermal and mechanical stimuli using, respectively, a plantar test apparatus and von Frey filaments, before and after adult LPS. Expression of dorsal root ganglion and lumbar spinal cord COX-2 was also examined. Animals treated as neonates with saline showed the expected hypersensitivity to painful stimuli after adult LPS as well as enhanced spinal cord COX-2. Neonatally LPS-treated rats, however, showed a significantly different profile. They displayed enhanced baseline nociception and elevated basal spinal cord COX-2 compared with neonatally saline-treated rats. Also, rather than the expected hyperalgesia after adult LPS, no changes in nociceptive responses and a reduction in spinal cord COX-2 expression were observed. These findings have important implications for the understanding of pain and its management and highlight the importance of the neonatal period in the development of pain pathways.
Publisher: Society for Neuroscience
Date: 13-03-2013
DOI: 10.1523/JNEUROSCI.4241-12.2013
Abstract: Serotonin has a myriad of central functions involving mood, appetite, sleep, and memory and while its release within the spinal cord is particularly important for generating movement, the corresponding role on cortical movement representations (motor maps) is unknown. Using adult rats we determined that pharmacological depletion of serotonin (5-HT) via intracerebroventricular administration of 5,7 dihydroxytryptamine resulted in altered movements of the forelimb in a skilled reaching task as well as higher movement thresholds and smaller maps derived using high-resolution intracortical microstimulation (ICMS). We ruled out the possibility that reduced spinal cord excitability could account for the serotonin depletion-induced changes as we observed an enhanced Hoffman reflex (H-reflex), indicating a hyperexcitable spinal cord. Motor maps derived in 5-HT 1A receptor knock-out mice also showed higher movement thresholds and smaller maps compared with wild-type controls. Direct cortical application of the 5-HT 1A/7 agonist 8-OH-DPAT lowered movement thresholds in vivo and increased map size in 5-HT-depleted rats. In rats, electrical stimulation of the dorsal raphe lowered movement thresholds and this effect could be blocked by direct cortical application of the 5-HT 1A antagonist WAY-100135, indicating that serotonin is primarily acting through the 5-HT 1A receptor. Next we developed a novel in vitro ICMS preparation that allowed us to track layer V pyramidal cell excitability. Bath application of WAY-100135 raised the ICMS current intensity to induce action potential firing whereas the agonist 8-OH-DPAT had the opposite effect. Together our results demonstrate that serotonin, acting through 5-HT 1A receptors, plays an excitatory role in forelimb motor map expression.
Publisher: American Physiological Society
Date: 2007
DOI: 10.1152/AJPREGU.00398.2006
Abstract: Early life events and childhood infections have been associated with the development and onset of inflammatory bowel disease in adulthood. However, the consequences of neonatal infection in the development and severity of colitis are not established. We investigated the effects of a neonatal (postnatal day 14) or juvenile (postnatal day 28) immune challenge with LPS on 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced damage and weight loss, as well as on food intake and body temperature in adult rats. Neonatally (n)LPS-treated rats developed more severe colitis than control animals, reflected in a greater loss of weight and a significantly increased macroscopic tissue damage score. These findings were associated with a hypothermic response after TNBS treatment in nLPS rats, but not in neonatally saline-treated rats receiving TNBS. These differences were not seen after TNBS in rats that had received LPS on postnatal day 28. Plasma corticosterone was measured as an index of adult hypothalamic-pituitary-adrenal (HPA) axis activation as was TNF-α, a proinflammatory cytokine associated with inflammatory bowel disease. Four days after TNBS treatment, plasma corticosterone was unaltered in all groups however, TNF-α was significantly increased in adult TNBS-treated rats that had LPS as neonates compared with all other groups. In conclusion, neonatal, but not later, exposure to LPS produces long-term exacerbations in the development of colitis in adults. This change is independent of HPA axis activation 4 days after TNBS treatment but is associated with increased circulating TNF-α, suggestive of an exaggerated immune response in adults exposed to neonatal infection.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2008
DOI: 10.1161/STROKEAHA.107.497016
Abstract: Background and Purpose— Stroke during pregnancy is an emerging concern. Although females undergo many physiological, endocrine, and neurological alterations during pregnancy, the consequences of such changes on outcome after stroke are unclear. It is predicted that increases in steroid hormones observed during pregnancy may confer protective effects against the neurological and pathological sequelae of stroke. Methods— We therefore investigated behavioral and histological consequences of a global cerebral ischemia (2-vessel occlusion 2VO), and how these outcomes correlated with pregnancy-related changes in hormones in Sprague-Dawley rats. Results— After the 2VO, pregnant rats exhibited poorer memory in a contextual fear conditioning test of learning and memory than sham-treated controls, whereas nonpregnant rats did not. They also showed enhanced CA1 hippoc al neuronal injury. This susceptibility to damage is despite significant pregnancy-associated hypothermia and is probably not associated with alterations in 17β-estradiol or corticosterone levels. Conclusion— These findings are the first to show enhanced neuronal damage in pregnant animals after global cerebral ischemia. They also suggest that the mechanism may be independent of changes in estrogen, corticosterone, and body temperature.
Publisher: Oxford University Press (OUP)
Date: 10-06-2009
DOI: 10.1093/ICB/ICP025
Publisher: Society for Neuroscience
Date: 09-06-2010
Publisher: Wiley
Date: 14-01-2008
No related grants have been discovered for Quentin Pittman.