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
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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DOI：
10.1016/j.yhbeh.2014.01.003
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发表时间：
2014-03-01
影响因子：
3.5
通讯作者：
Plamondon, Helene
中科院分区：
文献类型：
--
作者：
de la Tremblaye, Patricia B.;Raymond, Julie;Plamondon, Helene
神经内分泌应激系统的异常功能与脑缺血后观察到的行为障碍有关。本研究检测了全脑缺血后30天应激信号调节的长期变化。实验一观察了大鼠下丘脑室旁核（PVN）、杏仁中央核（CeA）和海马CM区促肾上腺皮质激素释放激素（CRH）及其受体1亚型（CRHR 1）、糖皮质激素受体（GR）表达的变化。在蓝斑（LC）测定酪氨酸羟化酶（TH）。实验2研究了暴露于急性应激源后，全脑缺血后多个时间间隔中枢CRHR 1激活对皮质酮（CURT）分泌的作用。实验一的结果表明，持续增加GR，CRH和CRHR 1免疫反应（IR）在PVN，减少GR和CRHRI表达锥体CA 1神经元，增加LC TH表达缺血大鼠显示工作记忆错误的桡侧臂迷宫。实验2的结果显示，缺血后7天内，GURT分泌增加，但在缺血后14天和21天不再存在。然而，在急性束缚应激诱导再灌注后27天，缺血大鼠血浆CURT分泌增加相比，假手术动物，表明HPA轴超敏反应。Antalarmin（2 pg/2 pl）预处理显著减弱缺血后基础和应激诱导的科里分泌升高。这些发现支持脑缺血后持续的神经内分泌功能障碍可能导致在心脏骤停和中风幸存者中观察到的情感和认知障碍。(C)2014爱思唯尔公司All rights reserved.
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 CM 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 (CURT) secretion at multiple time intervals following global ischemia after exposure to an acute stressor. Findings from Experiment I demonstrated a persistent increase in GR, CRH and CRHR1 immunoreactivity (ir) at the PVN, reduced GR and CRHRI 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 CURT 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 CURT secretions compared to sham-operated animals, suggesting HPA axis hypersensitivity. Antalarmin (2 pg/2 pl) pretreatment significantly attenuated post ischemic elevation of basal and stress-induced CORI 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. (C) 2014 Elsevier Inc. All rights reserved.