このエントリーをはてなブックマークに追加
ID 52804
フルテキストURL
著者
Kono, Syoichiro Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Neurol
Deguchi, Kentaro Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Neurol
Omote, Yoshio Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Neurol
Yunoki, Taijun Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Neurol
Yamashita, Toru Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Neurol ORCID Kaken ID
Kurata, Tomoko Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Neurol
Ikeda, Yoshio Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Neurol
Abe, Koji Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Neurol Kaken ID publons researchmap
抄録
This study assesses the risks and benefits of tissue plasminogen activator (tPA) treatment under oral anticoagulation with dabigatran compared with warfarin or vehicle control in transient middle cerebral artery occlusion (tMCAO). After pretreatment with warfarin (0.2 mg/kg/day), dabigatran (20 mg/kg/day), or vehicle (0.5% carboxymethyl cellulose sodium salt) for 7 days, tMCAO was induced for 120 min, followed by reperfusion and tPA (10 mg/kg/10 ml). Clinical parameters, including cerebral infarction volume, hemorrhagic volume, and blood coagulation, were examined. At 24 hr after reperfusion, markers for the neurovascular unit at the peri-ischemic lesion were immunohistochemically examined in brain sections, and MMP-9 activity was measured by zymography. Paraparesis and intracerebral hemorrhage volume were significantly improved in the dabigatran-pretreated group compared with the warfarin-pretreated group. A marked dissociation between astrocyte foot processes and the basal lamina or pericyte was observed in the warfarin-pretreated group, which was greatly improved in the dabigatran-pretreated group. Furthermore, a remarkable activation of MMP-9 in the ipsilateral warfarin-pretreated rat brain was greatly reduced in dabigatran-pretreated rats. The present study reveals that the mechanism of intracerebral hemorrhage with warfarin-pretreatment plus tPA in ischemic stroke rats is the dissociation of the neurovascular unit, including the pericyte. Neurovascular protection by dabigatran, which was first shown in this study, could partially explain the reduction in hemorrhagic complication by dabigatran reported from clinical study.
キーワード
dabigatran
hemorrhagic complication
neurovascular unit
pericyte
thrombolysis
tPA
発行日
2014-01
出版物タイトル
Journal of Neuroscience Research
92巻
1号
開始ページ
46
終了ページ
53
ISSN
0360-4012
資料タイプ
学術雑誌論文
関連URL
http://ousar.lib.okayama-u.ac.jp/metadata/52528
言語
English
著作権者
(c) 2013 Wiley Periodicals, Inc.
論文のバージョン
author
査読
有り
DOI
Web of Science KeyUT