医学
ADAMTS13号
血管性血友病因子
脑出血
组织纤溶酶原激活剂
脑血流
麻醉
缺血
冲程(发动机)
内科学
蛛网膜下腔出血
血小板
机械工程
工程类
作者
Takafumi Nakano,Keiichi Irie,Kazuhide Hayakawa,Kazunori Sano,Yoshihiko Nakamura,Masayoshi Tanaka,Yuta Yamashita,Tomomitsu Satho,Masayuki Fujioka,Carl Muroi,Koichi Matsuo,Hiroyasu Ishikura,Kojiro Futagami,Kenichi Mishima
出处
期刊:Brain Research
[Elsevier]
日期:2015-10-01
卷期号:1624: 330-335
被引量:21
标识
DOI:10.1016/j.brainres.2015.07.027
摘要
Tissue plasminogen activator (tPA) is the only approved therapy for acute ischemic stroke. However, delayed tPA treatment increases the risk of cerebral hemorrhage and can result in exacerbation of nerve injury. ADAMTS13, a von Willebrand factor (VWF) cleaving protease, has a protective effect against ischemic brain injury and may reduce bleeding risk by cleaving VWF. We examined whether ADAMTS13 has a longer therapeutic time window in ischemic stroke than tPA in mice subjected to middle cerebral artery occlusion (MCAO). ADAMTS13 (0.1mg/kg) or tPA (10mg/kg) was administered i.v., immediately after reperfusion of after 2-h or 4-h MCAO for comparison of the therapeutic time windows in ischemic stroke. Infarct volume, hemorrhagic volume, plasma high-mobility group box1 (HMGB1) levels and cerebral blood flow were measured 24h after MCAO. Both ADAMTS13 and tPA improved the infarct volume without hemorrhagic complications in 2-h MCAO mice. On the other hand, ADAMTS13 reduced the infarct volume and plasma HMGB1 levels, and improved cerebral blood flow without hemorrhagic complications in 4-h MCAO mice, but tPA was not effective and these animals showed massive intracerebral hemorrhage. These results indicated that ADAMTS13 has a longer therapeutic time window in ischemic stroke than tPA, and ADAMTS13 may be useful as a new therapeutic agent for ischemic stroke.
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