Evidence of lasting dysregulation of neuroendocrine and HPA axis function following global cerebral ischemia in male rats and the effect of Antalarmin on plasma corticosterone level |
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Authors: | Patricia B de la Tremblaye Julie Raymond Marc R Milot Zul Merali Hélène Plamondon |
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Institution: | 1. Behavioural Neuroscience Group, School of Psychology, University of Ottawa, 136 Jean-Jacques Lussier, Ottawa, ON, K1N 6N5, Canada;2. University of Ottawa Institute of Mental Health Research (IMHR), 1145 Carling Avenue Ottawa, Ontario K1Z 7K4, Canada |
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Abstract: | Abnormal function of the neuroendocrine stress system has been implicated in the behavioral impairments observed following brain ischemia. The current study examined long-term changes in stress signal regulation 30 days following global cerebral ischemia. Experiment 1 investigated changes in the expression of corticotropin releasing hormone (CRH) and its subtype 1 receptor (CRHR1), glucocorticoid receptors (GR) in the paraventricular nucleus of the hypothalamus (PVN), the central nucleus of the amygdala (CeA), and the CA1 subfield of the hippocampus. Tyrosine hydroxylase (TH) was determined at the locus coeruleus (LC). Experiment 2 investigated the role of central CRHR1 activation on corticosterone (CORT) secretion at multiple time intervals following global ischemia after exposure to an acute stressor. Findings from Experiment 1 demonstrated a persistent increase in GR, CRH and CRHR1 immunoreactivity (ir) at the PVN, reduced GR and CRHR1 expression in pyramidal CA1 neurons, and increased LC TH expression in ischemic rats displaying working memory errors in the radial arm Maze. Findings from Experiment 2 revealed increased CORT secretion up to 7 days, but no longer present 14 and 21 days post ischemia. However upon an acute restraint stress induced 27 days following reperfusion, ischemic rats had increased plasma CORT secretions compared to sham-operated animals, suggesting HPA axis hypersensitivity. Antalarmin (2 μg/2 μl) pretreatment significantly attenuated post ischemic elevation of basal and stress-induced CORT secretion. These findings support persistent neuroendocrine dysfunctions following brain ischemia likely to contribute to emotional and cognitive impairments observed in survivors of cardiac arrest and stroke. |
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Keywords: | HPA axis dysregulation post-ischemia |
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