The Mechanism of the Cerebral Vasospasm in a Rat Subarachnoid Hemorrhage Model. -Mechanistic Role of Cholesterol in the Regulation of Vasospasm-

YOSHINO Hiroko

doi:10.2342/ymj.63.123

Objective：Rho-kinase（ROK）-mediated vascular smooth muscle（VSM）contraction plays a pivotal role in cerebral vasospasm（CV）．Previous studies showed that hypercholesterolemia increased sphingosylphosphorylcholine-ROK-mediated VSM contraction. Lipid rafts and caveolae are cholesterol-enriched membrane microdomains that influence signal transduction. In this study, we showed the effect of cholesterol, lipid raft, and caveolae on CV.Methods：Sprague-Dawley rats received a control diet, a cholesterol-diet, or a cholesterol-diet+β-cyclodextrin, which depletes VSM cholesterol, for 8 weeks, and were subjected to SAH model surgery. We used double-hemorrhage SAH model, and CV of basilar artery（BA）at Day5 were measured using cranial window preparations. Total cholesterol levels in the internal carotid artery（ICA）were measured using gas chromatography. The expression of Flotilli-1, a planar raft marker, and Caveolin-1, a caveolae marker, in the ICA were analyzed by western blotting.Results：SAH-induced CV was markedly reversed by intracisternal infusion with Y27632（10μM），a ROK-inhibitor. Whereas the cholesterol-diet increased VSM cholesterol and CV, depletion of VSM cholesterol inhibited CV. The cholesterol-diet also increased Flotillin-1 and Caveolin-1 expression in the VSM. Depletion of VSM cholesterol also inhibited the increasing of Flotillin-1 and Caveolin-1 expression.Conclusions：These results indicate that cholesterol potentiates CV and are compatible with a role for lipid rafts and caveolae in this process.

The Mechanism of the Cerebral Vasospasm in a Rat Subarachnoid Hemorrhage Model. -Mechanistic Role of Cholesterol in the Regulation of Vasospasm-

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