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Roels of chemokines in ischemic brain injury

Research Project

Project/Area Number 13672280
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Biological pharmacy
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

MINAMI Masabumi  Kyoto University, Grad.Sch. of Pharmaceu. Sci., Assistant Professor, 薬学研究科, 助教授 (20243040)

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)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2002: ¥1,200,000 (Direct Cost: ¥1,200,000)
KeywordsChemokines / 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
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

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (19 results)

All Other

All Publications (19 results)

  • [Publications] 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)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamakuni, H.et al.: "ATP induces leukemia inhibitory factor mRNA in cultured rat astrocytes"J. Neuroimmunol.. 129. 43-50 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 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)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Katayama, T.et al.: "Excitotoxic injury induces production of monocyte chemoattractant protein-1 in rat cortico-striatal slice cultures"Neurosci. Lett.. 328. 277-280 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 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)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Minami, M.et al.: "Leukemia inhibitory factor induces nociceptin mRNA in cultured rat cortical neurons"Neurosci. Lett.. 311. 17-20 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamakuni,H. et al.: "ATP induces leukemia inhibitory factor mRNA in cultured rat astrocytes"J. Neuroimmunol.. 129. 43-50 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Katayama,T. et al.: "Excitotoxic injury induces production of monocyte chemoattractant protein-1 in rat cortico-striatal slice cultures"Neurosci. Lett.. 328. 277-280 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Minami,M. et al.: "Leukemia inhibitory factor induces nociceptin mRNA in cultured rat cortical neurons"Neurosci. Lett.. 311. 17-20 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 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)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yamakuni, H. et al.: "ATP induces leukemia inhibitory factor mRNA in cultured rat astrocytes"J. Neuroimmunol.. 129. 43-50 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 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)

    • Related Report
      2002 Annual Research Report
  • [Publications] 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)

    • Related Report
      2002 Annual Research Report
  • [Publications] Takami, S. et al.: "Chemokine receptor antagonist peptide, viral MIP-II, protects brain against cerebral ishchernia in mice"J. Cereb. Blood Flow Metab. 21. 1430-1435 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Minarni, M. et al.: "Leukemia inhibitory factor induces nociceptin mRNA in cultured rat cortical neurons"Neurosci. Lett.. 311. 17-20 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yanari, M.A. et al.: "Calbindin D28K overexpression protects striatal neurons from transient focal cerebral ischemia"Stroke. 32. 1028-1035 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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