Impact of simvastatin on microthrombosis in cortical after subarachnoid hemorrhage in rats and its mechanism

Abstract

Accumulating evidence demonstrates that subarachnoid hemorrhage (SAH)-induced microthrombosis plays important roles in the pathogenesis of delayed cerebral ischemia. The purpose of the present study was to determine the impact of simvastatin on microthrombi formation and cerebral vasospasm after SAH and explore its mechanism. A total of 24 adult male SD rats were divided into 4 groups: (1) control group (n = 6); (2) SAH group (n = 6); (3) SAH + vehicle group (n = 6) and (4) SAH + simvastatin group (n = 6). SAH was induced by injecting 0.3 ml of fresh arterial, non-heparinized blood into prechiasmatic cistern in 20 sec with a syringe pump. In the SAH + simvastatin group, simvastatin was administered ip at a dose of 20 mg×kg(-1)×d(-1) after SAH. Brain samples were excised after perfusion fixation at 7 days post-SAH. Microclots were evaluated by H&E staining. Microthrombi formation was measured by fibrinogen immunostaining. The number of microthrombi was 1 ± 1, 25 ± 5, 24 ± 4 and 5 ± 2 in control, SAH, vehicle and simvastatin groups respectively. The number of microthrombi significantly increased in cerebral cortex at 7 days post-SAH (P < 0.01). The treatment of simvastatin down-regulated the formation of microclots in the SAH model and the number of microthrombi decreased significantly in the SAH + simvastatin group as compared with the SAH or SAH + vehicle groups (P < 0.01). The administration of simvastatin alleviates microthrombosis in late phase of SAH in this prechiasmatic blood injection model.