title: Acute neurovascular unit protection by simvastatin in transient cerebral ischemia.
abstract: Acute vascular- and neuroprotective effects of simvastatin were evaluated in a rat model of transient, focal cerebral ischemia. Male, Wistar rats (n=12) underwent transient middle cerebral artery (MCA) occlusion for 3 hours followed by 3 hours of reperfusion. After 30 minutes of MCA occlusion, four rats each were subcutaneously injected with either 20 or 40 mg/kg of simvastatin. At the end of 3 hours of reperfusion, tissue injury and blood-brain barrier (BBB) opening were quantified by histology and [(14)C]-alpha-aminoisobutyric acid (AIB)-based quantitative autoradiography (QAR), respectively. Compared with untreated rats, those treated with simvastatin (20 mg/kg) had reduced volumes of AIB leakage, tissue pallor and distribution space for AIB (p<0.05). No additional effects were seen with the higher drug dose (40 mg/kg). These data suggest that the acute neuroprotective effects of statins are in part owing to attenuation of stroke-induced changes in BBB permeability.
authors.affiliation: Department of Anesthesiology, Henry Ford Health System, Detroit, MI 48202, USA. annta@neuro.hfh.edu
authors.forename: Tavarekere N
authors.initials: TN
authors.lastname: Nagaraja
authors.forename: Robert A
authors.initials: RA
authors.lastname: Knight
authors.forename: Richard L
authors.initials: RL
authors.lastname: Croxen
authors.forename: Kirthi P
authors.initials: KP
authors.lastname: Konda
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Fenstermacher
mesh_terms: D000621:Aminoisobutyric Acids / Q000378:metabolism; D000818:Animals; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D001345:Autoradiography; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D001929:Brain Edema / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D020520:Brain Infarction / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D002199:Capillary Permeability / Q000187:drug effects; D002247:Carbon Isotopes / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D004195:Disease Models, Animal; D007839:Functional Laterality; D002546:Ischemic Attack, Transient / Q000150:complications* / Q000473:pathology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D015424:Reperfusion / Q000009:adverse effects; D015427:Reperfusion Injury / Q000209:etiology / Q000517:prevention & control*; D019821:Simvastatin / Q000627:therapeutic use*
chemical_list: D000621:Aminoisobutyric Acids; D000924:Anticholesteremic Agents; D002247:Carbon Isotopes; C100049:2-aminoisobutyric acid; D002784:Cholesterol; D019821:Simvastatin