Neuroprotective properties of statins in cerebral ischemia and stroke

Background-The atheroma-retarding properties of beta-hydroxy-beta-methylglu taryl coenzyme A reductase (HMG-CoA) inhibitors, or "statins," in both the coronary and carotid arterial beds are well established. However, a growing body of recent data suggests that statins possess important adjunctive pro perties that may confer additional benefit beyond the retardation of athero sclerosis. In this article, we review the emerging evidence that statins ha ve beneficial effects within the cerebral circulation and brain parenchyma during ischemic stroke and reperfusion. Summary of Review-Clinical studies show that statins reduce the incidence o f ischemic stroke through probable effects on precerebral atherosclerotic p laque and through antithrombotic mechanisms. Additionally, statins have bee n shown to reduce infarct size in experimental animal models of stroke. Sta tins both upregulate endothelial nitric oxide synthase (eNOS) and inhibit i nducible nitric oxide synthase (iNOS), effects that are potentially neuropr otective. The preservation of eNOS activity in cerebral vasculature, partic ularly in the ischemic penumbra, may be especially important in preserving blood flow and limiting neurological loss. Statins may also attenuate the i nflammatory cytokine responses that accompany cerebral ischemia, and they p ossess antioxidant properties that likely ameliorate ischemic oxidative str ess in the brain. Conclusions-In addition to reducing stroke, the statin class of drugs exhib its a number of important neuroprotective properties that likely attenuate the effects of ischemia on the brain vasculature and parenchyma. Further in vestigation of the role of statins in human neuroprotection by use of neuro imaging and cognitive studies is warranted to explore these preliminary obs ervations. In addition to reducing ischemic stroke, early evidence indicate s that statins may also be neuroprotective.