Atorvastatin enhances hypothermia-induced neuroprotection after stroke

Abstract

BACKGROUND: Both statin and hypothermia protect the brain from focal cerebral ischemia. In this study, we sought to determine whether statin pretreatment enhances the efficacy of hypothermia and extends the therapeutic time window of hypothermia. METHODS: Rats were subjected to focal cerebral ischemia for 2 h. Initially, we tested the efficacy of atorvastatin pretreatment (1 mg/kg, daily for 10 days before ischemia) and hypothermia (32-33 degrees C for 2 h at onset of ischemia) in combination, and then we examined the effects of atorvastatin pretreatment on the therapeutic time window of hypothermia (3 or 6 h after ischemia). RESULTS: Both atorvastatin (27.5+/-4.6) and hypothermia (25.9+/-6.3%) reduced infarct volumes significantly as compared with the control group (40.5+/-3.3%; p<0.05 in each comparison). These two treatments in combination further decreased infarct volumes (13.2+/-6.3%), and remarkably reduced the staining extents of Ox-42, and of inducible nitric oxide synthase. In addition, hypothermia alone was found to be effective when applied at 3 h after ischemia, but not when applied at 6 h. However, atorvastatin pretreatment and hypothermia led to a significant reduction in infarct volumes even when hypothermia was applied at 6 h. CONCLUSIONS: It was found that atorvastatin pretreatment strongly enhances hypothermia-induced neuroprotection and extends the treatment window after stroke. Because both treatments are already known to be clinically feasible and safe, such a strategy would appear have merits for the treatment of acute stroke.