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

据报道，在各种病理条件下大脑中都会产生趋化因子及其受体。在这项研究中，我们发现侧脑室内和静脉注射 TAK-779（一种 CCR2/CCR5 选择性趋化因子受体拮抗剂）可减少梗塞体积。此外，静脉注射 TAK-779 减少了缺血半暗带中活化的巨噬细胞/小胶质细胞的数量，但不减少中性粒细胞的数量。这些发现表明，脑趋化因子在缺血性损伤中发挥着至关重要的作用，至少部分是通过增强白细胞浸润和小胶质细胞激活来实现的。脑趋化因子受体可能是中风治疗干预的目标抑制趋化因子有害作用的另一个潜在目标是调节缺血脑中趋化因子产生的信号传输系统。然而，人们对缺血性大脑中趋化因子的产生如何受到调节知之甚少。我们检查了皮质纹状体切片培养物中 ATPγS 或 NMDA 处理对 MCP-1 产生的诱导作用。 ATPγS直接作用于星形胶质细胞诱导MCP-1的产生。另一方面，NMDA首先作用于神经元，然后一些信号可能从受伤或兴奋的神经元发送到星形胶质细胞以诱导MCP-1的产生。这些结果表明，器官切片培养物有助于研究调节受损大脑中趋化因子产生的分子机制

项目成果

Takami, S.et al.: "Chemokine receptor antagonist peptide, viral MIP-II, protects brain against cerebral ishchemia in mice"J. Cereb. Blood Flow Metab.. 21. 1430-1435 (2001)

Takami, S.等人：“趋化因子受体拮抗剂肽，病毒 MIP-II，可保护小鼠大脑免受脑缺血”J.

Katayama, T. et al.: "Excitotoxic injury induces production of monocyte chemoattractant protein-I in rat cortico striatal slice cultures"Neurosci. Lett.. 328. 277-280 (2002)

Katayama, T. 等人：“兴奋毒性损伤诱导大鼠皮质纹状体切片培养物中单核细胞趋化蛋白-I 的产生”Neurosci。

Minami, M. et al.: "Kainic acid induces leukemia inhibitory factor mRNA expression in the rat brain : differences in the time course of mRNA expression between the dentate gyms and hippocampal CA1/CA3 subfields"Mol. Brain Res.. 107. 39-46 (2002)

Minami, M. 等人：“红藻氨酸在大鼠大脑中诱导白血病抑制因子 mRNA 表达：齿状体和海马 CA1/CA3 亚区之间 mRNA 表达时程的差异”Mol.

Yamakuni, H. et al.: "ATP induces leukemia inhibitory factor mRNA in cultured rat astrocytes"J. Neuroimmunol.. 129. 43-50 (2002)

Yamakuni, H. 等人：“ATP 在培养的大鼠星形胶质细胞中诱导白血病抑制因子 mRNA”J.

Minami, M.et al.: "Kainic acid induces leukemia inhibitory factor mRNA expression in the rat brain : differences in the time course of mRNA expression between the dentate gyrus and hippocampal CA1/CA3 subfields"Mol. Brain Res.. 107. 39-46 (2002)

Minami, M.等人：“红藻氨酸在大鼠大脑中诱导白血病抑制因子 mRNA 表达：齿状回和海马 CA1/CA3 亚区之间 mRNA 表达时程的差异”Mol.