Simvastatin and Atorvastatin Improve Neurological Outcome After Experimental Intracerebral Hemorrhage

Background and Purpose-This study investigates the effects of statin treatment on experimental intracerebral hemorrhage (ICH) using behavioral, histological, and MRI measures of recovery. Methods-Primary ICH was induced in rats. Simvastatin (2 mg/kg), atorvastatin (2 mg/kg), or phosphate-buffered saline (n = 6 per group) was given daily for 1 week. MRI studies were performed 2 to 3 days before ICH, and at 1 to 2 hours and 1, 2, 7, 14, and 28 days after ICH. The ICH evolution was assessed via hematoma volume measurements using susceptibility-weighted imaging (SWI) and tissue loss using T-2 maps and hematoxylin and eosin (H&E) histology. Neurobehavioral tests were done before ICH and at various time points post-ICH. Additional histological measures were performed with doublecortin neuronal nuclei and bromodeoxyuridine stainings. Results-Initial ICH volumes determined by SWI were similar across all groups. Simvastatin significantly reduced hematoma volume at 4 weeks (P = 0.002 versus control with acute volumes as baseline), whereas that for atorvastatin was marginal (P = 0.09). MRI estimates of tissue loss (% of contralateral hemisphere) for treated rats were significantly lower (P = 0.0003 and 0.001, respectively) than for control at 4 weeks. Similar results were obtained for H&E histology (P = 0.0003 and 0.02, respectively). Tissue loss estimates between MRI and histology were well correlated (R-2 = 0.764, P < 0.0001). Significant improvement in neurological function was seen 2 to 4 weeks post-ICH with increased neurogenesis observed. Conclusions-Simvastatin and atorvastatin significantly improved neurological recovery, decreased tissue loss, and increased neurogenesis when administered for 1 week after ICH. (Stroke. 2009;40:3384-3389.)