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Involvement of thrombin and mitogen-activated protein kinase pathways in hemorrhagic brain injury
http://hdl.handle.net/2298/10013
http://hdl.handle.net/2298/100137945af0f-6cf6-4d8d-a804-430fa30a071b
| 名前 / ファイル | ライセンス | アクション |
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Exp Neu0206-0043.pdf (758.9 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 | Involvement of thrombin and mitogen-activated protein kinase pathways in hemorrhagic brain injury | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| キーワード | ||||||
| 主題 | intracerebral hemorrhage, microglia, thrombin, mitogen-activated protein kinase, apoptosis | |||||
| 資源タイプ | ||||||
| 資源タイプ | journal article | |||||
| 著者 |
Ohnishi, Masatoshi
× Ohnishi, Masatoshi× 香月, 博志× 藤本, 真二× Takagi, Mikako× 久米, 利明× 赤池, 昭紀 |
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| 別言語の著者 |
大西, 正俊
× 大西, 正俊× 香月, 博志× 藤本, 真二× 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 | Thrombin is thought to play an important role in brain damage associated with intracerebral hemorrhage (ICH). We previously showed that activation of mitogen-activated protein (MAP) kinases and recruitment of microglia are crucial for thrombin-induced shrinkage of the striatal tissue in vitro and thrombin-induced striatal damage in vivo. Here we investigated whether the same mechanisms are involved in ICH-induced brain injury. A substantial loss of neurons was observed in the center and the peripheral region of hematoma at 3 days after ICH induced by intrastriatal injection of collagenase in adult rats. Intracerebroventricular injection of argatroban or cycloheximide, both of which prevent thrombin cytotoxicity in vitro, exhibited a significant neuroprotective effect against ICH-induced injury. ICH-induced neuron loss was also prevented by a MAP kinase kinase inhibitor (PD98059) and a c-Jun N-terminal kinase inhibitor (SP600125). These drugs had no effect on hematoma size or ICH-induced brain edema. Activation of extracellular signal-regulated kinase in response to ICH was observed in both neurons and microglia. Despite their neuroprotective effects, MAP kinase inhibitors did not decrease the number of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive cells appearing after ICH. Identification of cell types revealed that TUNEL staining occurred prominently in neurons but not in microglia, whereas inhibition of MAP kinases resulted in appearance of TUNEL staining in microglia. These results suggest that thrombin and the activation of MAP kinases are involved in ICH-induced neuronal injury, and that neuroprotective effects of MAP kinases are in part mediated by arrestment of microglial activities. | |||||
| 書誌情報 |
Experimental Neurology 巻 206, 号 1, p. 43-52, 発行年 2007-07 |
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| ISSN | ||||||
| 収録物識別子 | 00144886 | |||||
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| 収録物識別子タイプ | NCID | |||||
| 収録物識別子 | AA00641190 | |||||
| DOI | ||||||
| 関連タイプ | isVersionOf | |||||
| 関連識別子 | 10.1016/j.expneurol.2007.03.030 | |||||
| 権利 | ||||||
| 権利情報 | © 2007 Elsevier Inc. All rights reserved. | |||||
| フォーマット | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | application/pdf | |||||
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| 758923 bytes | ||||||
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| 出版タイプ | AM | |||||
| 日本十進分類法 | ||||||
| 主題Scheme | NDC | |||||
| 主題 | 491.17 | |||||
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| 出版者 | Elsevier Inc. | |||||
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| 内容記述タイプ | Other | |||||
| 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 | ||||||
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| 関連タイプ | isPartOf | |||||
| 識別子タイプ | URI | |||||
| 関連識別子 | http://hdl.handle.net/2298/9868 | |||||
| URL | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | http://www.elsevier.com/wps/find/journaldescription.cws_home/622828/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.117-126に掲載 | ||||||
