Abstract
Background: Microthrombosis and reactive inflammation contribute to neuronal injury after sub- arachnoid hemorrhage (SAH). ADAMTS-13 cleaves von Willebrand factor multimers, and inhibits thrombus formation and, seemingly, inflammatory reactions.
Objective: To investigate the effect of ADAMTS-13 in experi- mental SAH.
Methods: 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; 100 lL per 10 g of body weight of 100 lg of ADAMTS-13 per 1 mL of 0.9% NaCl; 20 min after SAH). Neurologic performance was assessed on days 1 and 2 after SAH. Animals were killed on day 2. The amounts of subarachnoid blood, microthrombi, apoptosis and degenerative neurons were compared. The degree of neuronal inflammation and vasospasm was also com- pared. In five mice each (SAH and ADAMTS-13 groups), bleeding time was assessed 2 h after SAH.
Results: 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 ten- dency for decreased neuronal inflammation was observed. ADAMTS-13 did not show any significant effect on vaso- spasm. 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.
Conclusions: ADAMTS-13 may reduce neuronal injury after SAH by reducing micro- thrombosis formation and neuronal inflammation, thereby providing a new option for mitigating the severity of neuronal injury after SAH.
Muroi, C