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线粒体功能和大脑中动脉闭塞时脑血流的可变反应。

Mitochondrial function and cerebral blood flow variable responses to middle cerebral artery occlusion.

机构信息

The Mina & Everard Goodman Faculty of Life-Sciences and the Gonda Multidisciplinary Brain Research Center Bar-Ilan University, Ramat-Gan, Israel.

出版信息

J Neurosci Methods. 2010 Apr 30;188(1):76-82. doi: 10.1016/j.jneumeth.2010.01.022. Epub 2010 Jan 28.

DOI:10.1016/j.jneumeth.2010.01.022
PMID:20109493
Abstract

Middle cerebral artery occlusion (MCAO), which leads to focal cerebral ischemia, serves as an experimental model for brain stroke. There is a large variation in protocols and techniques using the MCAO model, which may affect the outcomes seen in different studies. The current work presents and compares the diverse responses in mitochondrial NADH and cerebral blood flow (CBF) following focal ischemia induced by the MCAO technique. Ninety-six Wistar rats underwent focal cerebral ischemia by MCAO, and monitored in the core and the penumbra using a unique Multi-Site-Multi-Parametric (MSMP) system, which measures mitochondrial NADH using the fluorometric technique, and CBF using laser Doppler flowmetry (LDF). Following MCAO, 58% of the experiments yielded expected responses, namely a decrease in CBF and an increase in NADH. However, 42% of the experiments showed six other profiles of responses, in which CBF, NADH and tissue reflectance (Ref) responded differently. These profiles included: ischemia without reperfusion, death following reperfusion, minor responses in parameters during ischemia, CBF elevation in the penumbra following MCAO, spontaneous early reperfusion and late reperfusion. These results demonstrate that MCAO is a complex model, which may lead to different responses other than the common expected outcomes, i.e. mitochondrial damage and reduced blood flow in both core and penumbra. The MSMP monitoring system may serve as an important tool in early diagnosis of successful focal cerebral ischemia, reducing the percentage of unsuccessful experiments.

摘要

大脑中动脉阻塞(MCAO)导致局灶性脑缺血,是脑卒中等疾病的实验模型。在 MCAO 模型中,实验方案和技术存在很大差异,这可能会影响不同研究中的结果。目前的工作介绍并比较了 MCAO 技术诱导局灶性缺血后,线粒体 NADH 和脑血流(CBF)的不同反应。96 只 Wistar 大鼠通过 MCAO 发生局灶性脑缺血,并使用独特的多部位-多参数(MSMP)系统在核心和半影区进行监测,该系统使用荧光技术测量线粒体 NADH,使用激光多普勒血流仪(LDF)测量 CBF。MCAO 后,58%的实验产生了预期的反应,即 CBF 降低和 NADH 增加。然而,42%的实验显示了六种其他反应谱,其中 CBF、NADH 和组织反射率(Ref)反应不同。这些谱包括:无再灌注的缺血、再灌注后的死亡、缺血期间参数的轻微反应、MCAO 后半影区 CBF 升高、自发性早期再灌注和晚期再灌注。这些结果表明 MCAO 是一个复杂的模型,可能导致除核心和半影区线粒体损伤和血流减少等常见预期结果之外的不同反应。MSMP 监测系统可能成为早期诊断成功局灶性脑缺血的重要工具,降低不成功实验的比例。

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