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The Neuroscientist, Vol. 13, No. 3, 208-213 (2007)
DOI: 10.1177/1073858406297121
© 2007 SAGE Publications

Statins: Multiple Mechanisms of Action in the Ischemic Brain

Mauro Cimino

Institute of Pharmacology and Pharmacognosy, University of Urbino "Carlo Bo," Urbino, Italy

Paolo Gelosa

Department of Pharmacological Sciences, University of Milan, Milan, Italy

Anita Gianella

Department of Pharmacological Sciences, University of Milan, Milan, Italy

Elena Nobili

Department of Pharmacological Sciences, University of Milan, Milan, Italy

Elena Tremoli

Department of Pharmacological Sciences, University of Milan, Milan, Italy, Monzino Cardiologic Center IRCCS, Milan, Italy

Luigi Sironi

Department of Pharmacological Sciences, University of Milan, Milan, Italy, luigi.sironi{at}unimi.it

Although substantial epidemiological studies have failed to find a correlation between cholesterol levels and stroke, clinical trials have shown that HMG-CoA reductase inhibitors (or statins, the most potent hypocholesterolemic drugs available) greatly reduce the incidence of stroke. These clinical observations have opened the way to a number of studies of the non—cholesterol-dependent (or pleiotropic) effects in animal models of stroke, indicating that the neuroprotection is attributable to multiple activities. One of the main protective mechanisms elicited by statin administration is the increase in nitric oxide bioavailability that regulates cerebral perfusion and improves endothelial function, but others include antioxidant properties, the inhibition of inflammatory responses, immunomodulatory actions, the regulation of progenitor cells, and the stabilization of atherosclerotic plaques. Many of these effects are due to the inhibited synthesis of isoprenoid intermediates, which serve as lipid attachments for a variety of intracellular signaling molecules. This article describes the mechanisms involved in the neuroprotective effects of statins. NEUROSCIENTIST 13(3):208—213, 2007.

Key Words: Statin • Cerebral ischemia • Animal models • Nitric oxide


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