(Stroke. 1999;30:1969-1973.)
© 1999 American Heart Association, Inc.
Comments, Opinions, and Reviews |
Neuroprotective Properties of Statins in Cerebral Ischemia and Stroke
From the Division of Cardiology, Department of Medicine, Weill Medical College of Cornell University, The New York Presbyterian Hospital, New York, NY (C.J.V.), and Department of Neurology, Hospital of the University of Pennsylvania, Philadelphia, Pa (N.D.).
Correspondence to Carl J. Vaughan, MD, Cardiology Division, Department of Medicine, Weill Medical College of Cornell University, The New York Presbyterian Hospital, Starr 4, 525 E 68th St, New York, NY 10021. E-mail cvaughan{at}nyhs.med.cornell.edu
Background—The atheroma-retarding properties of ß-hydroxy-ß-methylglutaryl 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 properties that may confer additional benefit beyond the retardation of atherosclerosis. In this article, we review the emerging evidence that statins have 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 of ischemic stroke through probable effects on precerebral atherosclerotic plaque and through antithrombotic mechanisms. Additionally, statins have been shown to reduce infarct size in experimental animal models of stroke. Statins both upregulate endothelial nitric oxide synthase (eNOS) and inhibit inducible nitric oxide synthase (iNOS), effects that are potentially neuroprotective. The preservation of eNOS activity in cerebral vasculature, particularly in the ischemic penumbra, may be especially important in preserving blood flow and limiting neurological loss. Statins may also attenuate the inflammatory cytokine responses that accompany cerebral ischemia, and they possess antioxidant properties that likely ameliorate ischemic oxidative stress in the brain.
Conclusions—In addition to reducing stroke, the statin class of drugs exhibits a number of important neuroprotective properties that likely attenuate the effects of ischemia on the brain vasculature and parenchyma. Further investigation of the role of statins in human neuroprotection by use of neuroimaging and cognitive studies is warranted to explore these preliminary observations. In addition to reducing ischemic stroke, early evidence indicates that statins may also be neuroprotective.
Key Words: endothelium • HMG-CoA reductase inhibitors • inflammation • nitric oxide • neuroprotection
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