title: Simvastatin reduced ischemic brain injury and perfusion deficits in an embolic model of stroke.
abstract: Simvastatin is cholesterol lowering agent and also a modulator of cytokine in the nervous system. The functional significance and neuroprotectiove mechanism of simvastatins in ischemic brain injury is controversial. The purpose of study is to evaluate the effect of simvastatin on ischemic brain injury and to investigate the perfusion capability of brain microvessels in the ischemic injury. This study included two series of experiments. In the first series, we studied if simvastatin is neuroprotective in an embolic model of stroke. The treatments began 2 weeks before middle cerebral artery (MCA) occlusion. Infarct volume was measured at 48 h post stroke. Neurological deficits were assessed at 2 h, 24 h and 48 h post stroke. Results showed that infarct volume in rats which received saline and simvastatin was 32.5 +/- 9.3% (mean +/- SD) and 18.7 +/- 6.5%, respectively. The infarct volume in the simvastatin group was significantly smaller than in the controls (P < 0.002). Treatment with simvastatin also improved neurological deficits and reduced brain edema significantly (P < 0.05). In the second series, we studied if simvastatin can improve microvascular reperfusions after ischemia. Perfusion deficits were detected at 8 h post stroke using Evens blue dye. Neurological deficits were assessed at 2 h and 8 h post stroke. Results showed that perfusion deficit in saline and simvastatin-treated groups were 58.7 +/- 8.7% and 23.4 +/- 7.5%, respectively. The perfusion deficit in simvastatin-treated group was decreased 61% (P < 0.01). These studies thus suggest that simvastatin is a protective agent in ischemic brain injury and this protective effect may be partially due to its action in the improvement of microvascular reperfusion.
authors.affiliation: Stroke Research Laboratory, 533 HMRC, University of Alberta, Edmonton, Canada ABT6G 2S2.
authors.forename: Alireza P
authors.initials: AP
authors.lastname: Shabanzadeh
authors.forename: Ashfaq
authors.initials: A
authors.lastname: Shuaib
authors.forename: Chen Xu
authors.initials: CX
authors.lastname: Wang
mesh_terms: D000818:Animals; D001921:Brain / Q000098:blood supply / Q000473:pathology; D002545:Brain Ischemia / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D020766:Intracranial Embolism / Q000150:complications / Q000188:drug therapy*; D008297:Male; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015424:Reperfusion; D019821:Simvastatin / Q000627:therapeutic use*; D020521:Stroke / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D018696:Neuroprotective Agents; D019821:Simvastatin