2002 Fiscal Year Final Research Report Summary
Roels of chemokines in ischemic brain injury
| Project/Area Number |
13672280
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
MINAMI Masabumi Kyoto University, Grad.Sch. of Pharmaceu. Sci., Assistant Professor, 薬学研究科, 助教授 (20243040)
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| Co-Investigator(Kenkyū-buntansha) |
NAMURA Shobu National Cardiovascular Center, Stroke and Brain Protection Lab. and Dept. of Neurosurgery, 放射線医学部・心血管撮影研究室, 研究室長 (30311450)
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| Project Period (FY) |
2001 – 2002
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| Keywords | Chemokines / Chemokine receptors / Ischemia / Neuronal cell death / Astrocyte / Microglia / MCP-1 / Cortico-striatal slice cultures |
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| Research Abstract |
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 stroke
Another 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
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