title: Simvastatin blocks blood-brain barrier disruptions induced by elevated cholesterol both in vivo and in vitro.
abstract: Background. Hypercholesterolemia and disruptions of the blood brain barrier (BBB) have been implicated as underlying mechanisms in the pathogenesis of Alzheimer's disease (AD). Simvastatin therapy may be of benefit in treating AD; however, its mechanism has not been yet fully understood. Objective. To explore whether simvastatin could block disruption of BBB induced by cholesterol both in vivo and in vitro. Methods. New Zealand rabbits were fed cholesterol-enriched diet with or without simvastatin. Total cholesterol of serum and brain was measured. BBB dysfunction was evaluated. To further test the results in vivo, rat brain microvascular endothelial cells (RBMECs) were stimulated with cholesterol in the presence/absence of simvastatin in vitro. BBB disruption was evaluated. Results. Simvastatin blocked cholesterol-rich diet induced leakage of Evan's blue dye. Cholesterol content in the serum was affected by simvastatin, but not brain cholesterol. Simvastatin blocked high-cholesterol medium-induced decrease in TEER and increase in transendothelial FITC-labeled BSA Passage in RBMECs. Conclusions. The present study firstly shows that simvastatin improves disturbed BBB function both in vivo and in vitro. Our data provide that simvastatin may be useful for attenuating disturbed BBB mediated by hypercholesterolemia.
authors.affiliation: Department of Pathology, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China.
authors.forename: Xijuan
authors.initials: X
authors.lastname: Jiang
authors.forename: Maojuan
authors.initials: M
authors.lastname: Guo
authors.forename: Jinling
authors.initials: J
authors.lastname: Su
authors.forename: Bin
authors.initials: B
authors.lastname: Lu
authors.forename: Dongming
authors.initials: D
authors.lastname: Ma
authors.forename: Ruifeng
authors.initials: R
authors.lastname: Zhang
authors.forename: Lin
authors.initials: L
authors.lastname: Yang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
authors.forename: Yiwen
authors.initials: Y
authors.lastname: Ma
authors.forename: Yingchang
authors.initials: Y
authors.lastname: Fan