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Induction and Identification of Endogenous Anti-Ischemic Mechanisms (Factors)

内源性抗缺血机制（因子）的诱导和鉴定

基本信息

批准号：
63440058
负责人：
SHIMOJI Koki
金额：
$ 9.22万
依托单位：
Nigata University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (A)
财政年份：
1988
资助国家：
日本
起止时间：
1988 至 1991
项目状态：
已结题

项目摘要

We have previously suggested that artificial minor brain injury induces certain endogenous anti-ischemic mechanisms in the mouse brain. In this study, we examined the survival rate of mice following brain ischemia and characterized the endogenous anti-ischemic activities induced by minor brain injury. The survival rates following incomplete brain ischemia was improved during 1 to 2 weeks following artificial brain injury in the mice. Artificial brain injury also improved the survival from the lidocain-induced seizure. Post-ischemic increase in regional metabolic activity was attenuated in the injured mouse brain. The direct injection of nerve growth factor (NGF), one of neurotropic factors, into the brain tissue did not improve the survival rate of the mice following brain ischemia. On the other hand, we found that Ca^<2+> overload in cytosol may relate to irreversible dysfunction of neurons in hippocampal slices exposed to hypoxia and the increase in intracellular free Ca^<2+> concentration induced by hypoxia in the absence of glucose was attenuated in the vicinity of lesion site in hippocampal CA1 region of mouse brain slices. The results suggest that the anti-ischemic mechanisms may be activated during 1 to 2 weeks in the recovering process from brain injury and may be protective against lidocaine-induced seizure and hypermetabolism following brain ischemia. The origin of anti-ischemic activity may be not assigned to NGF, but certain factor (s) may be produced in the lesion site to attenuate the increase in intracellular free Ca^<2+> concentration, protecting the ischemic cell damage.

我们以前曾提出，人工轻微脑损伤诱导某些内源性抗缺血机制的小鼠大脑。在这项研究中，我们检查了小鼠脑缺血后的存活率，并表征了轻微脑损伤诱导的内源性抗缺血活性。在人工脑损伤后1 ~ 2周内，小鼠不完全脑缺血后的存活率有所提高。人工脑损伤也提高了利多卡因诱导癫痫发作的存活率。缺血后局部代谢活动的增加在损伤的小鼠脑中减弱。脑组织内直接注射神经生长因子（NGF）不能提高脑缺血小鼠的存活率。另一方面，我们发现细胞内Ca^2+超载可能与缺氧引起的海马脑片神经元不可逆性功能障碍有关，并且在小鼠脑片海马CA 1区损伤部位附近，无糖缺氧引起的细胞内游离Ca^2+浓度升高被减弱。结果提示，在脑损伤后1 ~ 2周的恢复过程中，抗缺血机制可能被激活，对利多卡因诱发的癫痫发作和脑缺血后的高代谢具有保护作用。抗缺血活性的来源可能不是NGF，但在损伤部位可能产生某些因子以减弱细胞内游离Ca^2+浓度的增加，从而保护缺血性细胞损伤。