Atorvastatin ameliorates early brain injury after subarachnoid hemorrhage via inhibition of AQP4 expression in rabbits

Abstract

The therapeutic effects of atorvastatin on early brain injury (EBI), cerebral edema and its association with aquaporin 4 (AQP4) were studied in rabbits after subarachnoid hemorrhage (SAH) using western blot analysis and the dry-wet method. Seventy-two healthy male New Zealand rabbits weighing between 2.5 and 3.2 kg were randomly divided into three groups: the SAH group (n=24), sham-operated group (n=24) and the SAH + atorvastatin group (n=24). A double SAH model was employed. The sham-operated group were injected with the same dose of saline solution, the SAH + atorvastatin group received atorvastatin 20 mg/kg/day after SAH. All rabbit brain samples were taken at 72 h after the SAH model was established successfully. Brain edema was detected using the dry-wet method after experimental SAH was induced; AQP4 and caspase-3 expression was measured by western blot analysis, and neuronal apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) staining at 72 h after SAH. The results indicated that brain edema and injury appeared soon after SAH, while brain edema and EBI were ameliorated and increased behavior scores were noted after prophylactic use of atorvastatin. Compared with the SAH group, the level of AQP4 and the cerebral content of water was significantly decreased (P<0.01) by atorvastatin, and TUNEL staining and studying the expression of caspase-3 showed that the apoptosis of neurons was reduced markedly both in the hippocampus and brain cortex by atorvastatin. The results suggest that atorvastatin ameliorated brain edema and EBI after SAH, which was related to its inhibition of AQP4 expression. Our findings provide evidence that atorvastatin is an effective and well-tolerated approach for treating SAH in various clinical settings.