ADAMTS13 gene deletion aggravates ischemic brain damage: a possible neuroprotective role of ADAMTS13 by ameliorating postischemic hypoperfusion
ADAMTS13 gene deletion aggravates ischemic brain damage: a possible neuroprotective role of ADAMTS13 by ameliorating postischemic hypoperfusion
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DOI：
10.1182/blood-2009-06-230110
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发表时间：
2010-02-25
期刊：
影响因子：
20.3
通讯作者：
Nishio, Kenji
中科院分区：
文献类型：
--
作者：
Fujioka, Masayuki;Hayakawa, Kazuhide;Nishio, Kenji
脑缺血后再灌注引起血栓形成和微循环障碍，这取决于血小板糖蛋白Ib-von Willebrand因子（VWF）轴。由于ADAMTS 13切割VWF并限制血小板依赖性血栓生长，ADAMTS 13可能改善急性卒中中的缺血性脑损伤。我们研究了ADAMTS 13对缺血再灌注损伤的影响，使用30分钟的大脑中动脉闭塞模型在Adamts 13（-/-）和野生型小鼠。再灌注0.5小时后，与野生型小鼠相比，Adamts 13（-/-）小鼠缺血皮质局部脑血流量明显减少（P <0.05），这也导致Adamts 13（-/-）小鼠24小时后的梗死体积比野生型小鼠大（P <0.01）。因此，ADAMTS 13基因缺失加重了缺血性脑损伤，提示ADAMTS 13可能通过调节再灌注后VWF-血小板相互作用来保护脑免受缺血。这些结果表明ADAMTS 13可能是一种有用的治疗中风的药物。（血。2010;115：1650-1653）
Reperfusion after brain ischemia causes thrombus formation and microcirculatory disturbances, which are dependent on the platelet glycoprotein Ib-von Willebrand factor (VWF) axis. Because ADAMTS13 cleaves VWF and limits platelet-dependent thrombus growth, ADAMTS13 may ameliorate ischemic brain damage in acute stroke. We investigated the effects of ADAMTS13 on ischemia-reperfusion injury using a 30-minute middle cerebral artery occlusion model in Adamts13(-/-) and wild-type mice. After reperfusion for 0.5 hours, the regional cerebral blood flow in the ischemic cortex was decreased markedly in Adamts13(-/-) mice compared with wild-type mice (P < .05), which also resulted in a larger infarct volume after 24 hours for Adamts13(-/-) compared with wild-type mice (P < .01). Thus, Adamts13 gene deletion aggravated ischemic brain damage, suggesting that ADAMTS13 may protect the brain from ischemia by regulating VWF-platelet interactions after reperfusion. These results indicate that ADAMTS13 may be a useful therapeutic agent for stroke. (Blood. 2010;115:1650-1653)