Possible Involvement of P2X_7 Receptor Activation in Microglial Neuroprotection against Focal Cerebral Ischemia in Rats(Pharmacology)
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概要
- 論文の詳細を見る
Microglia play important roles in the pathogenic cascade following cerebral ischemia, since they express growth factors, chemokines and regulatory cytokines as well as free radicals and other toxic mediators. P2X_7 receptor, a subtype of a family of P2 purinoceptors, is primarily expressed in microglia and macrophages, suggesting that it regulates immune function and inflammatory responses. However, the involvement of ATP in such microglial responses after cerebral ischemia is not yet understood. In this study, we investigated the possible involvement of ATP, especially through the P2X_7 receptors, in a rat model of focal cerebral ischemia. In immunohistochemical analysis, P2X_7 receptor-like immunoreactivity was predominantly detected in microglia, and then activated microglia accumulated in the ischemic region, in rats subjected to middle cerebral artery occlusion (MCAO) and reperfusion. Intracerebroventricular injection with P2X_7 receptor agonist 2'-3'-O-(4-benzoylbenzoyl)adenosine 5'-triphosphate (BzATP) improved behavioral dysfunction accessed by rota-rod test and ischemic neural injury induced by MCAO. In contrast, P2X_7 receptor antagonist adenosine 5'-triphosphate-2',3'-dialdehyde (OxATP) exacerbated ischemic brain damage. These results suggest that microglia play an important role in neuroprotection against rat cerebral ischemia, which is regulated by a P2X_7 receptor-mediated ATP signal.
- 公益社団法人日本薬学会の論文
- 2008-06-01
著者
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Takata Kazuyuki
Faculty Of Pharmaceutical Sciences Hoshi University
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Taniguchi Takashi
Department of Geophysics, Faculty of Science, Hokkaido University
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Taniguchi T
Department Of Neurobiology Kyoto Pharmaceutical University
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Takahashi Kazunori
京都薬科大学 病態生理学
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Taniguchi Takashi
京都薬科大学 病態生理学
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KITAMURA Yoshihisa
Department of Neuropharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University
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Nakata Yoshihiro
Department of Pharmacology, Hiroshima University Graduate School of Biomedical Sciences, Japan
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Hide Izumi
Department of Molecular and Pharmacological Neuroscience, Graduate School of Biomedical Sciences, Hi
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Yanagisawa Daijiro
Department Of Neurobiology Kyoto Pharmaceutical University
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TAKATA Kazuyuki
Department of Neurobiology, Kyoto Pharmaceutical University
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Takata Kazuyuki
Department Of Mechanical Engineering Aichi Institute Of Technology
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Nakata Yoshihiro
Graduate School Of Biomedical Sciences Hiroshima Univ.
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Takeuchi Kosei
Kan Research Institute Inc. Kobe Mi R&d Center
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Takenawa Tadaomi
Division Of Biochemistry Institute Of Medical Science University Of Tokyo
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Nakata Yoshihiro
Department Of Pharmacology Graduate School Of Biomedical Sciences Hiroshima University
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Kanai Yoshihito
Department Of Pharmaceutical Care And Health Sciences Okayama University Graduate School Of Medicine
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Kitamura Yoshihisa
Department Of Neurobiology Kyoto Pharmaceutical University
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Kitamura Yoshihisa
Department Of Pharmacology Research Institute For Wakan-yaku Toyama Medical And Pharmaceutical Unive
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Kitamura Y
Department Of Neurobiology Kyoto Pharmaceutical University
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Kitamura Y
Shimizu Pharmaceutical Co. Ltd. Shizuoka Jpn
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Taira Takahiro
Graduate School Of Pharmaceutical Sciences Hokkaido University:crest Japan Science And Technology Co
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Hide Izumi
Department Of Pharmacology Graduate School Of Biomedical Sciences Hiroshima University
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Nakata Yoshihiro
Department Of Biophysics Gunma University
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Takano T
Dep. Of Neurobiology Kyoto Pharmaceutical Univ.
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Taniguchi Takashi
Department Of Geophysics Faculty Of Science Hokkaido University
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Hide Izumi
Department Of Molecular And Pharmacological Neuroscience Graduate School Of Biomedical Sciences Hiro
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Nakata Yoshihiro
Dep. Of Pharmacology Hiroshima Univ. Graduate School Of Biomedical Sciences Jpn
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Taniguchi Takashi
Department Of Dermatology Faculty Of Medicine University Of Tokyo
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Takata Kazuyuki
Department of Clinical and Translational Physiology, Kyoto Pharmaceutical University
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TANIGUCHI Takashi
Department of Computational Science and Engineering, Nagoya University
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Kitamura Yoshihisa
Department of Clinical Pharmacy, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Japan
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Taniguchi Takashi
Department of Biology, Kyoto Pharmaceutical University
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KITAMURA Yoshihisa
Department of Clinical Pharmacy, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University
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