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(Stroke. 2007;38:3251.)
© 2007 American Heart Association, Inc.

Original Contributions

Delayed Postischemic Treatment With Fluvastatin Improved Cognitive Impairment After Stroke in Rats

Munehisa Shimamura, MD, PhD; Naoyuki Sato, MD, PhD; Masataka Sata, MD, PhD; Hitomi Kurinami, MD; Daisuke Takeuchi, MD; Kouji Wakayama, MD; Takuya Hayashi, MD, PhD; Hidehiro Iida, MD, PhD Ryuichi Morishita, MD, PhD

From Department of Advanced Clinical Science and Therapeutics (M.S., M.Sata, K.W.), Graduate School of Medicine, the University of Tokyo, Japan; Department of Clinical Gene Therapy (N.S., H.K., D.T., R.M.), Graduate School of Medicine, Osaka University, Japan; Department of Investigative Radiology (T.H., H.I.), National Cardiovascular Center, Research Institute, Japan.

Correspondence to Ryuichi Morishita, MD, PhD, Professor, Division of Clinical Gene Therapy, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita 565-0871, Japan. E-mail morishit{at}cgt.med.osaka-u.ac.jp

Background and Purposes— Recent clinical evidences indicate that statins may have beneficial effects on the functional recovery after ischemic stroke. However, the effect of delayed postischemic treatment with statins is still unclear. In the present study, we evaluated the effects of fluvastatin in the chronic stage of cerebral infarction in a rat model.

Methods— Rats exposed to permanent middle cerebral artery occlusion were treated for 3 months with fluvastatin beginning from 7 days after stroke. MRI, behavioral analysis, and immunohistochemistry were performed.

Results— Two months of treatment with fluvastatin showed the significant recovery in spatial learning without the decrease in serum total cholesterol level and worsening of infarction. Microangiography showed a significant increase in capillary density in the peri-infarct region in fluvastatin-treated rats after 3 months of treatment. Consistently, BrdU/CD31-positive cells were significantly increased in fluvastatin-treated rats after 7 days of treatment. MAP1B-positive neurites were also increased in the peri-infarct region in fluvastatin-treated rats. In addition, rats treated with fluvastatin showed the reduction of superoxide anion after 7 days of treatment and the reduction of Aß deposits in the thalamic nuclei after 3 months of treatment.

Conclusions— Thus, delayed postischemic administration of fluvastatin had beneficial effects on the recovery of cognitive function without affecting the infarction size after ischemic stroke. Pleiotropic effects of fluvastatin, such as angiogenesis, neuritogenesis, and inhibition of superoxide production and Aß deposition, might be associated with a favorable outcome.

Key Words: angiogenesis • cerebral infarct • microcirculation • statins