title: Intravenous rosuvastatin for acute stroke treatment: an animal study.
abstract: OBJECTIVE
  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.
authors.affiliation: Klinik und Polikinik für Neurologie, Charité Universitätsmedizin Berlin, Campus Mitte, Charitéplatz 1, D-10117 Berlin, Germany.
authors.forename: Vincent
authors.initials: V
authors.lastname: Prinz
authors.forename: Ulrich
authors.initials: U
authors.lastname: Laufs
authors.forename: Karen
authors.initials: K
authors.lastname: Gertz
authors.forename: Golo
authors.initials: G
authors.lastname: Kronenberg
authors.forename: Mustafa
authors.initials: M
authors.lastname: Balkaya
authors.forename: Christoph
authors.initials: C
authors.lastname: Leithner
authors.forename: Ute
authors.initials: U
authors.lastname: Lindauer
authors.forename: Matthias
authors.initials: M
authors.lastname: Endres
mesh_terms: D000208:Acute Disease; D000818:Animals; D001011:Aorta / Q000201:enzymology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005464:Fluorobenzenes / Q000097:blood / Q000494:pharmacology*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000097:blood / Q000494:pharmacology*; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000473:pathology; D007275:Injections, Intravenous; D051379:Mice; D008815:Mice, Inbred Strains; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011743:Pyrimidines / Q000097:blood / Q000494:pharmacology*; D020127:Recovery of Function / Q000187:drug effects; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000097:blood / Q000494:pharmacology*
chemical_list: D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011743:Pyrimidines; D013449:Sulfonamides; D000068718:Rosuvastatin Calcium; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; D051057:Proto-Oncogene Proteins c-akt