Roels of chemokines in ischemic brain injury

趋化因子及其受体在大脑中的产生在各种病理条件下已被报道。在这项研究中，我们发现脑室内和静脉注射TAK-779（一种CCR2/ CCR5选择性趋化因子受体拮抗剂）可减少梗死体积。此外，静脉注射TAK-779可减少缺血半暗区活化的巨噬细胞/小胶质细胞的数量，但不影响中性粒细胞的数量。这些发现表明，脑趋化因子在缺血性损伤中起着至关重要的作用，至少在一定程度上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脑卒中治疗干预的靶点。抑制趋化因子有害作用的另一个潜在靶点是调节缺血脑中趋化因子产生的信号传递系统。然而，对于缺血脑中趋化因子的产生是如何调节的，我们知之甚少。我们在皮质纹状体切片培养中检测了atp - γ s或NMDA处理对MCP-1产生的诱导作用。atp - γ s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，然后可能从受损或兴奋的神经元向星形胶质细胞发送一些信号，诱导MCP-1的产生。这些结果表明，器官型切片培养有助于研究损伤脑中趋化因子产生的分子机制

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