Eszopiclone Prevents Excitotoxicity and Neurodegeneration in the Hippocampus Induced by Experimental Apnea
Eszopiclone Prevents Excitotoxicity and Neurodegeneration in the Hippocampus Induced by Experimental Apnea
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DOI：
10.1093/sleep/32.12.1593
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发表时间：
2009-12-01
期刊：
影响因子：
5.6
通讯作者：
Chase, Michael H.
中科院分区：
文献类型：
--
作者：
Fung, Simon J.;Xi, Ming-Chu;Chase, Michael H.
研究目的：本研究旨在确定右佐匹克隆对呼吸暂停诱导的兴奋性毒性突触过程和海马细胞凋亡的影响。设计：在麻醉豚鼠中诱导呼吸暂停的复发期，包括一系列呼吸暂停（75%SpO（2）），随后恢复到正常氧（> 95%SpO（2））的通气，持续3小时。刺激海马CA 3 Schaffer侧支通路，记录CA 1区的场兴奋性突触后电位（fEPSP）反应。实验组动物在复发性呼吸暂停期开始前10分钟接受右佐匹克隆（3 mg/kg）静脉注射，此后每60分钟注射一次;对照组动物接受相当的溶媒注射。在反复呼吸暂停的3小时结束时，对动物进行灌注，并对海马切片进行免疫染色以确定细胞凋亡的存在，即，分析和结果：呼吸暂停导致CA 1神经元的突触反应性的持续增加，如通过fEPSP的分析所确定的。右佐匹克隆拮抗呼吸暂停诱导的fEPSP增加形态学分析显示，在对照动物的CA 1神经元的显着凋亡，但是，没有显着的凋亡在右佐匹克隆治疗animals.Conclusions：右佐匹克隆被确定为抑制呼吸暂停诱导的海马CA 1神经元的过度兴奋，从而减少/消除神经毒性。这些数据证实了我们的假设，即右佐匹克隆（不包括其催眠作用）有能力作为一种有效的神经保护剂。
Study Objective: This study was designed to determine the effects of eszopiclone on apnea-induced excitotoxic synaptic processes and apoptosis in the hippocampus.Design: Recurrent periods of apnea, which consisted of a sequence of apnea (75% SpO(2)), followed by ventilation with recovery to normoxia (>95% SpO(2))' were induced for a period of three hours in anesthetized guinea pigs. The CA3 Schaffer collateral pathway in the hippocampus was stimulated and the field excitatory postsynaptic potential (fEPSP) response was recorded in CA1. Animals in the experimental group received an intravenous injection of eszopiclone (3 mg/kg) 10 min prior to the initiation of the periods of recurrent apnea, and once every 60 min thereafter; control animals received comparable injections of vehicle. At the end of the 3-h period of recurrent apnea, the animals were perfused, and hippocampal sections were immunostained in order to determine the presence of apoptosis, i.e., programmed cell death.Analyses and Results: Apnea resulted in a persistent increase in synaptic responsiveness of CA1 neurons as determined by analyses of the fEPSP. Eszopiclone antagonized the apnea-induced increase in the fEPSP Morphological analyses revealed significant apoptosis of CA1 neurons in control animals; however, there was no significant apoptosis in eszopiclone-treated animals.Conclusions: Eszopiclone was determined to suppress the apnea-induced hyperexcitability of hippocampal CA1 neurons, thereby reducing/eliminating neurotoxicity. These data lend credence to our hypothesis that eszopiclone, exclusive of its hypnotic actions, has the capacity to function as a potent neuroprotective agent.