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

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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.