Statins excert neuroprotection on cerebral ischemia independent of their lipid-lowering action: the potential molecular mechanisms.

Cerebral ischemia is a major neurological disorder and a leading cause of death and disability in the world. Statins are a widely used group of cholesterol-lowering agents that act by inhibiting the enzyme 3-hydroxy 3-methylglutaryl CoA (HMG CoA) reductase, which catalyses the rate-limiting step of cholesterol biosynthesis. In addition to their cholesterol-lowering properties, however, statins exert a number of so-called 'pleiotropic' actions. Data has emerged largely from thromboembolic animal models of stroke and cultivated cells. It is suggested that statins which have efficacy in preventing the stroke pretreatedly may have a positive effect even given post ischemia possibly through their pleiotropic effects. Mechanisms of the protective actions on cerebral ischemia include the inhibition of inflammatory responses, the improvement of endothelial dysfunction, the regulation of apoptosis proteins, the reduction of oxidative damage and the control of other relative endogenous signal pathways. Attempting to review these properties of statins is an exciting work that will improve our understanding on stroke and thus enable us to better use clinically this type of drugs. The present review summarizes available evidences on the effects and the potential molecular mechanisms of statins on cerebral ischemia.