Efficacy of Combined Atorvastatin and Sildenafil in Promoting Recovery After Ischemic Stroke in Mice

Abstract

The aim of this study was to test the hypothesis that a combination of atorvastatin and sildenafil promotes recovery in an additive manner after ischemic stroke in mice. Adult C57BL/6 mice (n = 67) were subjected to transient middle cerebral artery occlusion. Vehicle-control (H2O), atorvastatin (0.3 mg/kg), sildenafil (0.3 mg/kg), or combined atorvastatin (0.3 mg/kg) and sildenafil (0.3 mg/kg) were administrated via oral gavage daily for 6 days starting 24 hrs after ischemia. Behavioral studies including neurologic score and adhesive removal test were performed before surgery and on postoperative days 1 and 7; cylinder test was performed before surgery and on postoperative day 7. Mice were killed after 7 days and brain slices were stained with hematoxylin and eosin to measure the infarct volume. The combination group performed significantly better in the adhesive removal test (mean ± SD) (50 ± 54 secs) as compared with the control group (147 ± 109 secs) (P < 0.05) and to atorvastatin (144 ± 102 secs) (P < 0.05) but did not show statistically significant improvement as compared with sildenafil (107 ± 115 secs) (P = 0.148). There were no significant differences among the groups in neurologic score and cylinder test. There was no significant difference in the infarct volume. The data suggest that combined atorvastatin and sildenafil generates a better functional outcome as compared with atorvastatin-only treatment, but not sildenafil-only treatment, in one of multiple variables tested.