Abstract 1944: Atorvastatin Reduces Intracerebral Hemorrhage after Experimental Stroke
Ischemic stroke is a leading cause of death and disability in the United States and diabetes mellitus is the fastest growing risk factor for stroke. In addition, hyperglycemia, which is usually associated with diabetes, tends to worsen ischemia/reperfusion injury and to induce more oxidative stress damage. Preliminary data from our laboratory showed that diabetic animals (Goto-Kakizaki rats (GKs) are more susceptible to vascular damage leading to intracerebral hemorrhage. Many studies have indicated that statins possess neuroprotective properties even when administered after the onset of ischemia. However, the acute vascular effects of statins after ischemic stroke have not been studied to date.
Objective: to evaluate the efficacy and magnitude of vascular protection of acute statin therapy in both GKs and their normoglycemic controls after experimental ischemic stroke.
Methods: Male Wistar (W) and GK rats (270–305 g) underwent 3 hours of middle cerebral artery occlusion (MCAO) followed by reperfusion for 21 hours. Animals were randomized to receive either atorvastatin (15mg/Kg) or methyl cellulose (0.5%), administered by oral gavage, the first dose 5 minutes after reperfusion and the second dose after 12 hours. Brain tissue was analyzed for infarct volume and hemoglobin content. In another set of Wistar rats (n=3), atorvastatin (15mg/Kg) was administered by oral gavage to compare its pharmacokinetic profile with that of humans
Results: Atorvastatin-treated groups had significantly lower hemoglobin (p=0.0156) and infarct volume (p=0.0132) compared to their controls. Atorvastatin peak concentration (27–77 ng/ml) in rats’ plasma was found to be similar to that seen after 80mg/day of atorvastatin in humans.
Conclusion: Atorvastatin can be a novel vascular protective agent after acute ischemic stroke especially in a high risk population like diabetics. The mechanisms through which these effects are mediated are currently being investigated.