Influence of simvastatin on microthrombosis in the brain after subarachnoid hemorrhage in rats: a preliminary study.

Although previous studies indicate that simvastatin can attenuate cerebral vasospasm after subarachnoid hemorrhage (SAH), its effect on the secondary pathophysiological changes after SAH has not been investigated. Accumulating evidence demonstrates that SAH-induced microthrombosis plays important roles in the pathogenesis of delayed cerebral ischemia. To date, however, no study focused on the treatment of microthrombosis in SAH models. The purpose of this study was to determine the impact of simvastatin on microthrombi formation after SAH in rats. Adult male SD rats were divided into four 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 the 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/d after SAH. Brain samples were excised after perfusion fixation at 7 days after SAH. The cross-sectional areas of the middle cerebral artery and anterior cerebral artery were measured. Microclots were evaluated by H&E staining. Microthrombi formation was measured by fibrin(ogen) immunostaining. The results showed that administration of simvastatin prevented vasospasm on day 7 following SAH (p <0.01). The number of microthrombi was significantly increased in both cerebral cortex and cerebellar cortex at 7 days after SAH (p <0.01). Simvastatin treatment down-regulated the formation of microclots in this SAH model and the number of microthombi was decreased significantly in the SAH+simvastatin group compared to the SAH or SAH+vehicle groups (p <0.01). In conclusion, simvastatin administration attenuates cerebral vasospasm and alleviates microthrombosis in the late phase of SAH in this prechiasmatic blood injection model.