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Basic studies for prevention and treatment of the ischemic neuronal death

缺血性神经元死亡防治的基础研究

基本信息

批准号：
08457374
负责人：
NAKAGOMI Tadayoshi
金额：
$ 4.16万
依托单位：
Teikyo Univ.School of Med.
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1998
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08457374/
关键词：
neuronal death ischemic tolerance multiple ischemia stress protein indomethacin brain temperature gerbil

项目摘要

The aim of this study was to investigate whether repetitive sublethal ischemia enhances isehemic tolerance or not. Seventy-two adult male Mongolian gerbils were used. Bilateral carotid arteries were occluded for 2 min to induce sublethal forebrain ischemia, or 4 min to induce lethal ischemia. Sublethal ischemia were given once or eight times (every 2 days or 4 days) to the animals 2 or 4 weeks before lethal ischemia. Seven days after lethal ischemic insult, the animals were perfusion-fixed, and the neuronal densities in the hippocampal CA1 sector were estimated. Twenty-eight animals were used for the immunohistological study. At 2w and 4 w following single or multiple sublethal ischemia (every 2 days) and at 2d following the lethal ischemia immunostaining of fixed gebil brain containing the dorsal hippocampus against HSP7O was performed. In gerbils with repetitive sublethal ischemia, neuronal density of the CA1 sector was significantly (p<O.05) higher at 4 weeks following the last sublethal ischemia than that of the animals with single sublethal ischemia. Induction of HSP7O was seen neither at 2w and 4 w following single or multiple sublethal ischemia (every 2 days) nor at 2d following the lethal ischemia. The present study revealed that repetitive sublethal ischemia enhances ischemic tolerance.In another experiment using 5-mm forebrain iscemia model, effect of indomethacin to the neuronal death in the hippocampal CA1 sector was studied. Indomethacin did not ameliorate neuronal death under the condition that kept brain temperature (temporal muscle temperature) at 37.5 0.5. This study delineated that protective effect of indomethacin to the ischemic neyronal injury is based on the lowering effect of brain temperature.

本研究的目的是探讨重复性亚致死性缺血是否能增强缺血耐受。使用72只成年雄性蒙古沙鼠。阻断双侧颈动脉2 min诱导亚致死性前脑缺血，4 min诱导致死性前脑缺血。在致死性缺血前2周或4周，对动物进行1次或8次亚致死性缺血（每2天或4天）。致死性缺血损伤后7天，将动物灌注固定，并估计海马CA 1区的神经元密度。28只动物用于免疫组织学研究。在单次或多次亚致死性脑缺血（每2天一次）后2周和4周以及致死性脑缺血后2d，对固定的含背侧海马的Gebil脑进行HSP 70免疫组化染色。在反复亚致死性缺血的沙鼠中，在最后一次亚致死性缺血后4周，CA 1区的神经元密度显著高于单次亚致死性缺血的动物（p<0.05）。在单次或多次亚致死性缺血（每2天一次）后2周和4周以及致死性缺血后2天均未观察到HSP 7 O的诱导。本实验采用5-mm前脑缺血模型，观察吲哚美辛对海马CA 1区神经元死亡的影响。吲哚美辛没有改善神经元死亡的条件下，保持大脑温度（颞肌温度）在37.5 - 0.5。本研究提示吲哚美辛对缺血性脑损伤的保护作用是基于其降低脑温的作用。