Statin pre-treatment protects brain against focal cerebral ischemia in diabetic mice.
BACKGROUND
Cerebrovascular diseases and other vascular complications are common and cause considerable mortality and morbidity in diabetes mellitus. Recent studies suggest that statins reduce the incidence of stroke in diabetic as well as non-diabetic patients. The outcome of stroke is shown to be worse in diabetics. However, the effect of statins on the outcome of stroke occurring in diabetics is not clear. The purpose of this study was to investigate the effect of pre-treatment with statins on focal cerebral ischemia in diabetic mice.


METHODS
Swiss albino mice were randomized into two groups. Diabetes was induced in the first group by intravenous streptozotosin injection. The second group served as non-diabetic. After 4 weeks, half of the mice in diabetic and non-diabetic groups were randomized to receive intraperitoneal simvastatin 1 mg/kg/day or saline treatment for 14 days. Subsequently, mice were subjected to 90 min of proximal middle cerebral artery occlusion and 24 h of reperfusion. Sham-operation was also performed for each group. After 24 h of reperfusion, neurological deficits were scored and the infarct volume was measured on Nissl stained brain sections.


RESULTS
Infarct volume (median, interquartile range) was significantly increased in the diabetic group (60.7 mm(3)) compared to non-diabetic group (53.4 mm(3)). Statin pre-treatment significantly reduced the infarct volume (to 40.4; 33.5 mm(3), respectively) and neurological disability scores both in diabetic and non-diabetic groups.


CONCLUSIONS
These data suggest that diabetes aggravates the ischemic damage after focal cerebral ischemia and statin pre-treatment protects the brain in diabetic as well as healthy animals. Statin treatment may favorably affect stroke outcome in diabetic patients in addition to decreasing stroke incidence.
Cakmak
Atil
A
Department of General Surgery, Faculty of Medicine, Ankara University, Ankara, Turkey.
Yemişçi
Müge
M
Köksoy
Cüneyt
C
Yazgan
Uğur
U
Dinçer
Deniz
D
Dalkara
Turgay
T
D000818:Animals; D001921:Brain / Q000473:pathology; D002545:Brain Ischemia / Q000150:complications / Q000473:pathology / Q000517:prevention & control*; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000473:pathology / Q000517:prevention & control; D051379:Mice; D009043:Motor Activity; D009460:Neurologic Examination; D019821:Simvastatin / Q000494:pharmacology*
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019821:Simvastatin