HMG-CoA Reductase Inhibitor Has Protective Effects Against Stroke Events in Stroke-Prone Spontaneously Hypertensive Rats

Abstract

Background and Purpose— Recent clinical studies suggest that 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) exert protective effects against nonhemorrhagic stroke. In a murine cerebral ischemia model produced by occlusion of the middle cerebral artery, statins were shown to reduce infarct size. However, the effect of statins on hypertension-based stroke is unknown. The purpose of this study is to clarify the effect of a statin on stroke in stroke-prone spontaneously hypertensive rats (SHR-SP), in which both cerebral hemorrhage and infarction occur. Methods— We treated SHR-SP chronically from 4 weeks of age with cerivastatin (2 mg/kg per day by gavage) or vehicle. The physiological parameters, the incidence of stroke-associated symptoms, and mortality were assessed. Results— At 14 weeks of age, the incidence (13±3% versus 37±8%; P P P Conclusions— Our data show that a high dose of statin exerts protection against hypertension-based stroke and ameliorates the disease severity via inhibition of superoxide production and modulation of inflammation in brain.