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Intravenous rosuvastatin for acute stroke treatment: an animal study

Item Type:Article
Title:Intravenous rosuvastatin for acute stroke treatment: an animal study
Creators Name:Prinz, V. and Laufs, U. and Gertz, K. and Kronenberg, G. and Balkaya, M. and Leithner, C. and Lindauer, U. and Endres, M.
Abstract:BACKGROUND AND PURPOSE: Statins exert rapid cholesterol-independent vasoprotective effects. Here, we tested whether postevent treatment with intravenously (i.v.) administered rosuvastatin improves acute stroke outcome in mice. METHODS: 129/SV wild-type mice were subjected to 1-hour filamentous middle cerebral artery occlusion (MCAo), followed by reperfusion, and were postevent treated with i.v. or intraperitoneal (i.p.) rosuvastatin given up to 6 hours after MCAo (dose range 0.02 to 20 mg kg(-1) body weight). RESULTS: Rosuvastatin, when administered i.v., significantly reduced lesion size when given up to 4 hours after MCAo and in doses as low as 0.2 mg kg(-1). In contrast, i.p. administration provided protection only when given directly on reperfusion at a dose of 20 mg kg(-1) but not at lower doses or later time points. Lesion protection was evident as late as 5 days after brain ischemia and was associated with functional improvements in the pole-test and wire-hanging test (2.0 mg kg(-1) dose). Neuroprotection with i.v. rosuvastatin was achieved with peak plasma concentrations <0.5 ng ml(-1) (ie, with 0.2 mg kg(-1)) and was associated with increased levels of phosphorylated Akt kinase and endothelial nitric oxide synthase in the vasculature. CONCLUSIONS: Rosuvastatin, given intravenously at pharmacologically relevant concentrations, protects from focal brain ischemia up to 4 hours after an event. In our opinion, the development of an intravenous statin formulation is warranted for acute stroke trials with statins in humans.
Keywords:Acute Disease, Aorta, Animal Disease Models, Drug Dose-Response Relationship, Fluorobenzenes, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Middle Cerebral Artery Infarction, Intravenous Injections, Inbred Strains Mice, Nitric Oxide Synthase Type II, Phosphorylation, Proto-Oncogene Proteins c-akt, Pyrimidines, Recovery of Function, Reperfusion Injury, Sulfonamides, Animals, Mice
Publisher:Lippincott, Williams & Wilkins (U.S.A)
Page Range:433-438
Date:February 2008
Official Publication:https://doi.org/10.1161/STROKEAHA.107.492470
PubMed:View item in PubMed

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