A possible neuroprotective role of ADAMTS13 by ameliorating post-ischemic hypoperfusion

组织型纤溶酶原激活剂（t-PA）有时会引起缺血性中风的出血性并发症。vWF切割蛋白酶ADAMTS13通过调节vWF功能维持止血和溶栓的生理平衡。然而，ADAMTS13在脑缺血中的病理生理作用尚未被研究。在这项研究中，我们使用ADAMTS13敲除（KO）和野生型（WT）小鼠进行30分钟的大脑中动脉闭塞（MCAO）。再灌注24小时后，KO小鼠梗死面积和血浆炎症细胞因子HMGB1显著升高。此外，在WT小鼠中使用4小时mcao， ADAMTS13蛋白显著减少梗死体积，无出血并发症。但是，t-PA引起了大出血。这些结果表明，ADAMTS13通过调节血流和炎症而无出血性并发症，将成为缺血性卒中治疗的新途径。

Tissue plasminogen activator (t-PA) sometimes causes hemorrhagic complications in ischemic stroke. ADAMTS13, vWF-cleaving protease, maintains a physiologic balance between hemostasis and thrombolysis via regulation of vWF function. However, the pathophysiological role of ADAMTS13 in cerebral ischemia has not been investigated. In this study, we used ADAMTS13 knockout (KO) and Wild type (WT) mice subjected to 30 min of middle cerebral artery occlusion (MCAO). Infarct volume and plasma HMGB1 , inflammatory cytokine, was significantly increased at 24 hours after the reperfusion in KO mice. Further, ADAMTS13 protein significantly reduced the infarct volume without hemorrhagic complications using a 4hr-MCAO in WT mice. But, t-PA caused massive bleeding. These results indicate that ADAMTS13 would become a new therapeutic approach for ischemic stroke by regulating blood flow and inflammation without hemorrhagic complications.