Abstract WP256: Pretreatment of Rosuvastatin Ameliorates Early Brain Injury after Subarachnoid Hemorrhage through the Inhibition of Microglial Activation in Rats.

BACKGROUND AND PURPOSE: We investigated the protective effects of pretreatment of oral-administered rosuvastatin, a water soluble HMG-CoA reductase inhibitor, on early brain injury (EBI) after subarachnoid hemorrhage (SAH). METHOD: Male Sprague-Dawley rats were operated on with endovascular perforation model and randomly divided into 4 groups: sham-operated, SAH+vehicle, SAH+1mg/kg, or 10mg/kg rosuvastatin. The animals in treatment groups were administered with daily oral rosuvastatin from 7 days before to 1 day after operation. All rats were evaluated regarding neurofunction, brain edema, and blood-brain barrier (BBB) disruption at 24 hours after SAH. Anti-inflammatory responses were also conducted using Western blot and immunohistochemistry at 24 hours after SAH. RESULTS: Compared with the vehicle group, rosuvastatin significantly improved the neurofunction score (modified Garcia score/ 22: 13.0±1.6 vs 17.0±1.0, P P , and BBB disruption (IgG extravasation); data are showed as a mean±SEM. Rosuvastatin reduced number of activated microglial cells , activation of nuclear factor-kappa B(NF-kB), and expression of tumor necrosis factor-alpha (TNF-α) , which were considered as markers of inflammatory response from microglia, and downregulated the expression of neuronal cyclooxygenase-2 (COX-2) and endothelial matrix metalloproteinase-9 (MMP-9). CONCLUSION: The current study showed that pretreatment of rosuvastatin induced anti-inflammatory processes through inhibition of microglial activation and thereby attenuated early brain injury. Rosuvastatin seems to be a promising agent for treatment of SAH.