Efficacy of combined atorvastatin and sildenafil in promoting recovery after ischemic stroke in mice

OBJECTIVE: 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. DESIGN: Adult C57BL/6 mice (n = 67) were subjected to transient middle cerebral artery occlusion. Vehicle-control (H ₂O), 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. RESULTS: 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. CONCLUSIONS: 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.