Effect of ADAMTS‐13 on cerebrovascular microthrombosis and neuronal injury after experimental subarachnoid hemorrhage

Abstract

Microthrombosis and reactive inflammation contribute to neuronal injury after subarachnoid hemorrhage (SAH). ADAMTS-13 cleaves von Willebrand factor multimers, and inhibits thrombus formation and, seemingly, inflammatory reactions. To investigate the effect of ADAMTS-13 in experimental SAH. A total of 100 male C57/BL6 mice were randomly assigned to four groups: sham (n=15), SAH (n=27), vehicle (n=25), and ADAMTS-13 (n=23; 100μL per 10g of body weight of 100μg of ADAMTS-13 per 1mL of 0.9% NaCl; 20min after SAH). Neurologic performance was assessed on days1 and 2 after SAH. Animals were killed on day2. The amounts of subarachnoid blood, microthrombi, apoptosis and degenerative neurons were compared. The degree of neuronal inflammation and vasospasm was also compared. In five mice each (SAH and ADAMTS-13 groups), bleeding time was assessed 2h after SAH. Systemic administration of ADAMTS-13 achieved significant amelioration of microthrombosis and improvement in neurologic performance. ADAMTS-13 reduced the amount of apoptotic and degenerative neurons. A tendency for decreased neuronal inflammation was observed. ADAMTS-13 did not show any significant effect on vasospasm. The degree of systemic inflammation was not changed by ADAMTS-13 administration. ADAMTS-13 neither increased the amount of subarachnoid blood nor prolonged the bleeding time. ADAMTS-13 may reduce neuronal injury after SAH by reducing microthrombosis formation and neuronal inflammation, thereby providing a new option for mitigating the severity of neuronal injury after SAH.