Published Online
on May 27, 2004

A more recent version of this article appeared on July 1, 2004

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Submitted on January 23, 2004
Revised on March 10, 2004
Accepted on March 29, 2004

HMG-CoA Reductase Inhibitor, Atorvastatin, Promotes Sensorimotor Recovery, Suppressing Acute Inflammatory Reaction After Experimental Intracerebral Hemorrhage

Keun-Hwa Jung MD; Kon Chu MD; Sang-Wuk Jeong MD; So-Young Han MS; Soon-Tae Lee MD; Jin-Young Kim BS; Manho Kim MD, PhD; and Jae-Kyu Roh MD, PhD^*

From Stroke & Neural Stem Cell Laboratory in Clinical Research Institute (K.-H.J., K.C., S.-Y.H., S.-T.L., J.-Y.K., M.K., J.-K.R.), Department of Neurology, Seoul National University Hospital, Seoul National University, Seoul, South Korea; Department of Neurology (K.C.), Seoul National Hospital, Seoul, South Korea; Department of Neurology (S.-W.J.), Ilsan Paik Hospital, Inje University, Goyang, South Korea.

^* To whom correspondence should be addressed. E-mail: rohjk{at}snu.ac.kr.

Background and Purpose--Statins have neuroprotective effects on ischemic stroke. They modify the endothelial function, increase blood flow, and inhibit thrombus formation, which are independent of lipid-lowering effects. However, whether statins have a protective effect toward hemorrhagic stroke is yet unknown. To test this possibility, we attempted to determine the effect of atorvastatin on experimental intracerebral hemorrhage (ICH).

Methods--ICH was induced using stereotaxic infusion of collagenase into the left basal ganglia in adult rats. Atorvastatin (1 mg/kg or 10 mg/kg) or phosphate-buffered saline was administered for 2 weeks. To monitor the sensorimotor deficits, limb placing and Rotorod tests were performed. Hematoma volume, brain water content, and hemispheric atrophy were analyzed. Immunohistochemical staining for myeloperoxidase (MPO), microglia (OX42), inducible nitric oxide synthase (iNOS), or endothelial nitric oxide synthase (eNOS) was performed. Perihematomal cell death was determined by TUNEL staining.

Results--The atorvastatin-treated ICH group showed better performance on Rotorod and limb placing tests when compared with the vehicle-treated group (P<0.01). The hematoma volumes between groups were not different, but the brain water content and hemispheric atrophy were reduced in the atorvastatin-treated ICH group. Atorvastatin reduced TUNEL-positive cells, iNOS expression, and MPO-positive or OX42-positive cells in the perihematomal regions in a dose-dependent manner, whereas it increased eNOS expression.

Conclusion--The present study shows that atorvastatin reduces the perihematomal cell death via anti-inflammation, which is associated with sensorimotor recovery after experimental ICH.

Key words: HMG-CoA reductase inhibitors • intracerebral hemorrhage • brain edema • apoptosis • inflammation

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