@article{oai:kumadai.repo.nii.ac.jp:00021868, author = {藤本, 真二 and 香月, 博志 and 大西, 正俊 and 高木, 美佳子 and 久米, 利明 and 赤池, 昭紀 and 藤本, 真二 and Fujimoto, Shinji and 香月, 博志 and Katsuki, Hiroshi and Onishi, Masatoshi and Takagi, Mikako and 久米, 利明 and Kume, Toshiaki and 赤池, 昭紀 and Akaike, Akinori}, issue = {2}, journal = {Neuroscience}, month = {Jan}, note = {application/pdf, 論文(Article), 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., http://www.elsevier.com/wps/find/journaldescription.cws_home/468/description#description}, pages = {694--701}, title = {Thrombin induces striatal neurotoxicity depending on mitogen-activated protein kinase pathways in vivo}, volume = {144}, year = {2007}, yomi = {フジモト, シンジ and カツキ, ヒロシ and クメ, トシアキ and アカイケ, アキノリ} }