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ID 52804
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Author
Kono, Syoichiro
Omote, Yoshio
Yunoki, Taijun
Yamashita, Toru ORCID Kakenhi
Kurata, Tomoko
Ikeda, Yoshio
Abe, Koji Kakenhi
Abstract
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.
Keywords
dabigatran
hemorrhagic complication
neurovascular unit
pericyte
thrombolysis
tPA
Published Date
2014-01
Publication Title
Journal of Neuroscience Research
Volume
volume92
Issue
issue1
Start Page
46
End Page
53
ISSN
0360-4012
Content Type
Journal Article
Related Url
http://ousar.lib.okayama-u.ac.jp/metadata/52528
language
英語
Copyright Holders
(c) 2013 Wiley Periodicals, Inc.
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author
Refereed
True
DOI
Web of Science KeyUT