Roels of chemokines in ischemic brain injury

趋化因子在缺血性脑损伤中的作用

• 批准号: 13672280
• 负责人: MINAMI Masabumi
• 金额: $ 0.77万
• 依托单位: KYOTO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13672280/
• 关键词: Chemokines; Chemokine receptors; Ischemia; Neuronal cell death; Astrocyte; Microglia; MCP-1; Cortico-striatal slice cultures; ケモカイン受容体拮抗薬; 大脳皮質-線条体培養系; NMDA; サイトカイン

Production of chemokines and their receptors in the brain has been reported under various pathological conditions. In this study, we showed that intracerebroventricular and intravenous injections of TAK-779, a CCR2/ CCR5 selective chemokine receptor antagonist, reduced infarct volume. Furthermore, intravenous injection of TAK-779 decreased the number of activated macrophages/microglia, but not that of neutrophils, in the ischemic penumbra. These findings suggest that brain chemokines play a crucial role in ischemic injury, at least in part, by enhancing the leukocyte infiltration and microglia activation. Brain chemokine receptors might be the targets for therapeutic intervention in strokeAnother potential target to suppress the harmful effect of chemokines is the signal transmission system(s) regulating the chemokine production in the ischemic brain. However, very little is known about how the production of chemokines is regulated in the ischemic brain. We examined the induction of MCP-1 production by the treatment with ATPγS or NMDA in the cortico-striatal slice cultures. ATPγS directly acted on astrocytes to induce the MCP-1 production. On the other hand, NMDA acted on neurons at first, then some signal(s) is likely sent from the injured or excited neurons to astrocytes to induce the MCP-1 production. These results showed that organotypic slice cultures are useful to investigate the molecular mechanism regulating the chemokine production in the injured brain

在各种病理条件下，已经报道了趋化因子及其受体的产生。在这项研究中，我们表明脑室内和静脉注射TAK-779，CCR2/ CCR5选择性趋化因子受体拮抗剂，减少了梗塞体积。此外，静脉注射tak-779在缺血性半衰期中产生了活化巨噬细胞/小胶质细胞的数量，但不是中性粒细胞的数量。这些发现表明，脑趋化因子在缺血性损伤中至少通过增强白细胞浸润和小胶质细胞活化起着至关重要的作用。脑趋化因子接收器可能是抑制趋化因子的有害效应的strokeanother潜在靶标热干预的靶标，这是减少缺血性脑中趋化因子产生的信号传递系统。然而，关于趋化因子的产生如何在缺血性大脑中调节的知识知之甚少。我们检查了通过ATPγS或NMDA在Cortico-Striatal Slice培养物中使用ATPγS或NMDA的诱导MCP-1产生。 ATPγS直接作用于星形胶质细胞，以诱导MCP-1产生。另一方面，NMDA首先作用于神经元，然后一些信号从受伤或激发的神经元发送到星形胶质细胞以诱导MCP-1产生。这些结果表明，有机切片培养物可用于研究损伤大脑趋化因子产生的分子机制

项目成果

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Takami, S. et al.: "TAK-779, a nonpeptide CC chemokine receptor antagonist, protects the brain against focal cerebral ischemia in mice"J. Cereb. Blood Flow Metab.. 22. 780-784 (2002)

Takami, S. 等人：“TAK-779 是一种非肽 CC 趋化因子受体拮抗剂，可保护大脑免受小鼠局灶性脑缺血的影响”J.