Persistent behavioral impairments and neuroinflammation following global ischemia in the rat
Persistent behavioral impairments and neuroinflammation following global ischemia in the rat
复制标题
DOI：
10.1111/j.1460-9568.2008.06513.x
复制
发表时间：
2008-12-01
影响因子：
3.4
通讯作者：
Corbett, Dale
中科院分区：
文献类型：
--
作者：
Langdon, Kristopher D.;Granter-Button, Shirley;Corbett, Dale
与心脏骤停相关的认知缺陷已被充分记录;然而，尚未全面评估全脑缺血动物模型中的相应缺陷，特别是在长期临床相关生存期后。我们将雄性Sprague-Dawley大鼠暴露于10分钟的双侧颈动脉闭塞+全身性低血压（40-45 mmHg）或假手术，并对短期存活动物（16天）进行组织病理学评估，对长期存活动物（270天）进行行为和组织病理学评估。分析显示，缺血动物的学习、记忆（T-迷宫、径向臂迷宫）、工作记忆（径向臂迷宫）和参考记忆（莫里斯水迷宫、径向臂迷宫）能力存在显著的长期缺陷，这些缺陷与一般认知能力下降无关。组织学结果显示，缺血后16天，胶质细胞酸性蛋白、神经元胶质2、OX-42和艾德-1染色显著增加，微管相关蛋白2染色和角氨区1（CA 1）细胞计数显著减少。270天时的模式相似，但值得注意的是艾德-1染色持续升高，表明近期细胞死亡以及CA 1显著萎缩。而以前的工作主要报道了短暂的行为变化后，全脑缺血，这项研究描述了几个不同的功能域的干扰后，CA 1细胞损失在临床相关的生存时间。此外，组织病理学结果提示CA 1的自发再增殖，但这不足以抵消缺血性损伤引起的行为障碍。
Cognitive deficits associated with cardiac arrest have been well documented; however, the corresponding deficits in animal models of global ischemia have not been comprehensively assessed, particularly after long-term, clinically relevant survival times. We exposed male Sprague-Dawley rats to 10 min of bilateral carotid artery occlusion + systemic hypotension (40-45 mmHg) or sham surgery, and used histopathological assessments for short-term survival animals (16 days) and both behavioral and histopathological assessments for long-term survival animals (270 days). Analyses revealed significant long-term deficits in ischemic animals' learning, memory (T-maze, radial arm maze), working memory (radial arm maze), and reference memory (Morris water maze, radial arm maze) abilities that were not associated with a general cognitive decline. Histological results showed significant increases in glial fibrillary acidic protein, neuron glia 2, OX-42 and ED-1 staining, as well as significant decreases in microtubule-associated protein 2 staining and cornu ammonis area 1 (CA1) cell counts 16 days post-ischemia. The pattern at 270 days was similar, but notably there was a persistent elevation of ED-1 staining, suggesting recent cell death as well as significant atrophy of CA1. Whereas previous work has primarily reported transient changes in behavior after global ischemia, this study describes disturbances in several different functional domains following CA1 cell loss at clinically relevant survival times. Moreover, the histopathological outcome is suggestive of a spontaneous repopulation of CA1, but this was not sufficient to offset the behavioral impairments arising from the ischemic insult.