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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2003;23:322.)
© 2003 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Treatment With Statins After Induction of Focal Ischemia in Rats Reduces the Extent of Brain Damage

Luigi Sironi^*; Mauro Cimino^*; Uliano Guerrini; Anna Maria Calvio; Barbara Lodetti; Maria Asdente; Walter Balduini; Rodolfo Paoletti; Elena Tremoli

From the Department of Pharmacological Sciences (L.S., U.G., A.M.C., B.L., M.A., R.P., E.T.), Milan and Institute of Pharmacology and Pharmacognosy (M.C., W.B.), Urbino, Italy.

Correspondence to Elena Tremoli, Dipartimento di Scienze Farmacologiche, Università degli Studi di Milano, Via Balzaretti 9, I-20133 Milano, Italy. E-mail elena.tremoli{at}unimi.it

Objective— In the present study, MRI has been used to investigate therapeutic intervention with statins in a model of permanent focal cerebral ischemia in rat.

Methods and Results— Brain ischemia was induced in rats by the permanent occlusion of middle cerebral artery (MCAO) and the brain infarct size followed up in alive animals 2, 24, and 48 hours after MCAO, using the trace of apparent diffusion coefficient [Tr(D)] maps and T2-weighted images. In vehicle-treated rats, the infarct volumes increased by 38.5% and 89% after 24 and 48 hours, respectively, compared with the damage detected at 2 hours after MCAO. Treatment with simvastatin (20 mg/kg) after MCAO prevented the increase in brain infarct volume occurring at 24 hours and induced a 46.6% reduction after 48 hours. This effect was similar to that observed when simvastatin was administered before the induction of focal ischemia. T2W-MRI images confirmed these findings. The neuroprotective effects of simvastatin were paralleled by an increase in endothelial NO synthase immunoreactivity, detectable in the brain of simvastatin-treated rats.

Conclusions— Statins, in addition to their preventive effect on cerebral ischemia, exert a neuroprotective role in the attenuation of brain damage after acute stroke.

Key Words: statins • cerebral ischemia • rat • MRI • endothelial nitric oxide synthase

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