Delayed postischemic treatment with fluvastatin improved cognitive impairment after stroke in rats.
OBJECTIVE
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 A beta 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 A beta deposition, might be associated with a favorable outcome.
Shimamura
Munehisa
M
Department of Advanced Clinical Science and Therapeutics, Graduate School of Medicine, the University of Tokyo, Japan.
Sato
Naoyuki
N
Sata
Masataka
M
Kurinami
Hitomi
H
Takeuchi
Daisuke
D
Wakayama
Kouji
K
Hayashi
Takuya
T
Iida
Hidehiro
H
Morishita
Ryuichi
R
D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology; D003071:Cognition; D004195:Disease Models, Animal; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology*; D000077340:Fluvastatin; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007211:Indoles / Q000494:pharmacology*; D020244:Infarction, Middle Cerebral Artery / Q000175:diagnosis* / Q000473:pathology*; D007511:Ischemia; D008279:Magnetic Resonance Imaging / Q000379:methods; D009389:Neovascularization, Pathologic; D051381:Rats; D017208:Rats, Wistar; D020521:Stroke / Q000175:diagnosis* / Q000473:pathology*; D013481:Superoxides / Q000378:metabolism; D016896:Treatment Outcome
D000924:Anticholesteremic Agents; D005229:Fatty Acids, Monounsaturated; D007211:Indoles; D013481:Superoxides; D000077340:Fluvastatin