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Thrombin induces striatal neurotoxicity depending on mitogen-activated protein kinase pathways in vivo
http://hdl.handle.net/2298/10011
http://hdl.handle.net/2298/10011f11e6e9d-0bda-461c-85ce-88d61359f828
名前 / ファイル | ライセンス | アクション |
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Neuros0144-0694.pdf (401.7 kB)
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Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2008-12-02 | |||||
タイトル | ||||||
タイトル | Thrombin induces striatal neurotoxicity depending on mitogen-activated protein kinase pathways in vivo | |||||
言語 | ||||||
言語 | eng | |||||
キーワード | ||||||
主題 | apoptosis, intracerebral hemorrhage, microglia, microinjection, striatum | |||||
資源タイプ | ||||||
資源タイプ | journal article | |||||
著者 |
藤本, 真二
× 藤本, 真二× 香月, 博志× Onishi, Masatoshi× Takagi, Mikako× 久米, 利明× 赤池, 昭紀 |
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別言語の著者 |
藤本, 真二
× 藤本, 真二× 香月, 博志× 大西, 正俊× 高木, 美佳子× 久米, 利明× 赤池, 昭紀 |
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内容記述 | ||||||
内容記述 | Intracerebral hemorrhage represents stroke characterized by formation and expansion of hematoma within brain parenchyma. Blood-derived factors released from hematoma are considered to be involved in poor prognosis of this disorder. We previously reported that thrombin, a blood-derived serine protease, induced cytotoxicity in the cerebral cortex and the striatum in organotypic slice cultures, which depended on mitogen-activated protein kinase (MAPK) pathways. Here we investigated the mechanisms of thrombin cytotoxicity in the striatum in vivo. Thrombin microinjected into the striatum of adult rats induced neuronal death and microglial activation around the injection site. Neuronal loss without any sign of nuclear fragmentation was observed as early as 4 h after thrombin injection, which was followed by gradual neuronal death exhibiting nuclear fragmentation. Thrombin-induced damage assessed at 72 h after injection was partially but significantly reduced by concomitant administration of inhibitors of MAPK pathways. Activation of extracellular signal-regulated kinase (ERK) and p38 MAPK in response to thrombin was verified by Western blot analysis. Moreover, phosphorylated ERK and p38 MAPK were localized prominently in reactive microglia, and inhibition of microglial activation by minocycline attenuated thrombin-induced damage, suggesting that reactive microglia were responsible for thrombin-induced neuronal death. Thus, MAPK pathways and microglial activation may serve as therapeutic targets of pathogenic conditions associated with hemorrhagic stroke. | |||||
書誌情報 |
Neuroscience 巻 144, 号 2, p. 694-701, 発行年 2007-01-19 |
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ISSN | ||||||
収録物識別子 | 03064522 | |||||
書誌レコードID | ||||||
収録物識別子 | AA0075489X | |||||
DOI | ||||||
関連タイプ | isVersionOf | |||||
関連識別子 | 10.1016/j.neuroscience.2006.09.049 | |||||
権利 | ||||||
権利情報 | © 2006 IBRO Published by Elsevier Ltd. | |||||
フォーマット | ||||||
内容記述 | application/pdf | |||||
形態 | ||||||
401732 bytes | ||||||
著者版フラグ | ||||||
出版タイプ | AM | |||||
日本十進分類法 | ||||||
主題 | 491.17 | |||||
出版者 | ||||||
出版者 | International Brain Research Organization | |||||
資源タイプ | ||||||
内容記述 | 論文(Article) | |||||
資源タイプ・ローカル | ||||||
雑誌掲載論文 | ||||||
資源タイプ・NII | ||||||
Journal Article | ||||||
資源タイプ・DCMI | ||||||
text | ||||||
資源タイプ・ローカル表示コード | ||||||
01 | ||||||
部分である | ||||||
関連タイプ | isPartOf | |||||
関連識別子 | http://hdl.handle.net/2298/9868 | |||||
URL | ||||||
内容記述 | http://www.elsevier.com/wps/find/journaldescription.cws_home/468/description#description | |||||
コメント | ||||||
平成18~19年度科学研究費補助金(基盤研究(C))研究成果報告書 課題番号:18590052『ミクログリアの活性化を介する黒質線条体系ニューロン変性の機序とその防御』pp.80-87に掲載 |