Possible role of astrocytes in the disease progression of experimental cerebral ischemia

星形胶质细胞在实验性脑缺血疾病进展中的可能作用

基本信息

批准号：
14571330
负责人：
ASANO Takao
金额：
$ 2.05万
依托单位：
Saitama Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2004
项目状态：
已结题

项目摘要

The present study was undertaken to examine in terms of the following three aspects ; (i) the temporal as well as topographical correlation between the astrocytic S100B synthesis and the occurrence of delayed infarct expansion ; (ii) the analysis on the possible mechanisms underlying the S100B-induced brain damage ; (iii) the analysis on the possible therapeutic effects of an agent that suppresses astrocytic S100B synthesis on ischemic brain damage.1) In 2002, we focused on whether activated astrocytes accumulating within the peri-infarct area is related to the occurrence of delayed infarct expansion after ischemia. The results showed a positive temporal and topographical correlation between the enhanced synthesis of S-100B by activated astrocytes in the peri-infarct area and the occurrence of delayed infarct expansion.2) In 2003, using an astrocytic modulating agent, (P)-(-)-2-propyloctanoic acid (suppression of astrocytic activation through the negative regulation of S-100 protein sy … More nthesis), we examined the underlying mechanism(s) of delayed infarct expansion after ischemia. The results clearly showed that the enhanced astrocytic activation and subsequent production of S-100B protein in the peri-infarct area contribute to the occurrence of delayed infarct expansion.3) In 2004, to extend the possible clinical application of the agent against stroke, we examined the optimal dose and the therapeutic time window of the agent. The results showed the optimal dose of 10 mg/kg/day and a wide therapeutic time window ranging from 0 to 48 hours after ischemia.In summary, the present study contributed to substantiate the idea that activated astrocytes in the peri-infarct area do act to aggravate the ischemic brain damage during the subacute phase of permanent focal cerebral ischemia. We also demonstrated that suppression of astrocytic activation by the agent (R)-(-)-2-propyloctanoic acid (arundic acid) leads to mitigation of delayed infarct expansion and early improvement of neurological deficits. Based on the above data obtained from the consecutive studies during the past three years (2002 to 2004), we conclude that pharmacological modulation of astrocytic activation may confer a novel therapeutic strategy against stroke. Less

本研究是为了检查以下三个方面的研究。（i）星形细胞S100B合成与延迟感染扩张的发生之间的临时和地形相关性；（ii）对S100B诱导脑损伤的可能机制的分析；（iii）对抑制星形胶质细胞S100B合成对缺血性脑损伤的药物的可能治疗作用的分析。1）在2002年，我们集中于在缺血后的激活的星形胶质细胞中是否积累了积累的星形胶质细胞，与缺血后延迟的延迟性梗塞扩张的发生有关。结果表明，使用星形胶质细胞调节剂，（P） - （ - ） - 2- propopyloctanoic Action priptiation Syroctiation Syroction priptiatiation（ - ） n assis），我们检查了缺血后延迟感染扩张的基本机制。结果清楚地表明，增强的星形细胞活化和随后在侵蚀区域中S-100B蛋白的产生有助于发生延迟感染的扩张。3）2004年，为了扩展剂抗冲风的临床应用，我们检查了最佳剂量和药物的治疗时间窗口。结果表明，最佳剂量为10 mg/kg/day，局部率在0到48小时范围内。总而言之，本研究有助于证实，即在超含有永久性斑点斑点斑点斑点脑部的渗透症状上激活的星形胶质细胞确实会激活星形胶质细胞的作用。我们还证明，通过药剂（R） - （ - ） - 2-丙氯辛酸（Arundic Acid）抑制星形胶质细胞激活会导致减轻延迟感染扩张和神经系统缺陷的早期改善。基于过去三年（2002年至2004年）在连续研究中获得的上述数据，我们包括星形胶质细胞激活的药理学调节可以赋予针对中风的新型治疗策略。较少的