title: Pretreatment with rosuvastatin protects against focal cerebral ischemia/reperfusion injury in rats through attenuation of oxidative stress and inflammation.
abstract: This study aimed to examine the potential protective effect of rosuvastatin against cerebral ischemia/reperfusion injury and its mechanisms. Forty-eight male SD rats underwent 90 min of transient middle cerebral artery occlusion (tMCAO), followed by reperfusion. Rats were orally given (1) rosuvastatin 1mg/kg, (2) rosuvastatin 10mg/kg or (3) water (vehicle) once a day from 7 days before to 1 day after induction of tMCAO. Neurological score, infarct volume, and oxidative stress-related molecules (assessed by immunohistochemistry, dihydroethidium staining, or western blotting) were estimated at 24h after reperfusion. Rosuvastatin prevented the impairment of neurological function and decreased the infarct volume, compared with the vehicle group. The increases in activated microglia, macrophage, and superoxide levels usually caused by ischemia/reperfusion were significantly ameliorated by rosuvastatin. Rosuvastatin also inhibited the upregulation of gp91(phox) and p22phox, phosphorylation of nuclear factor-kappa B, and induction of cyclooxygenase 2 and inducible nitric oxide synthase, compared with vehicle. The results suggest that pretreatment with rosuvastatin may be a promising therapeutic strategy for cerebral ischemia/reperfusion injury, through attenuation of oxidative stress and inflammation.
authors: Department of Pharmacology and Molecular Therapeutics, Kumamoto University, Graduate School of Medical Sciences, Kumamoto, Japan.
authors: Mingjie
authors: M
authors: Ma
authors: Ken
authors: K
authors: Uekawa
authors: Yu
authors: Y
authors: Hasegawa
authors: Takashi
authors: T
authors: Nakagawa
authors: Tetsuji
authors: T
authors: Katayama
authors: Daisuke
authors: D
authors: Sueta
authors: Kensuke
authors: K
authors: Toyama
authors: Keiichiro
authors: K
authors: Kataoka
authors: Nobutaka
authors: N
authors: Koibuchi
authors: Jun-ichi
authors: J
authors: Kuratsu
authors: Shokei
authors: S
authors: Kim-Mitsuyama
mesh_terms: D000818:Animals; D020520:Brain Infarction / Q000209:etiology / Q000517:prevention & control; D002545:Brain Ischemia / Q000517:prevention & control*; D002135:Calcium-Binding Proteins / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D053331:Ectodysplasins / Q000378:metabolism; D004660:Encephalitis / Q000188:drug therapy* / Q000209:etiology; D005464:Fluorobenzenes / Q000008:administration & dosage*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D008840:Microfilament Proteins / Q000378:metabolism; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D011743:Pyrimidines / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control*; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000008:administration & dosage*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: C100745:Aif1 protein, rat; D002135:Calcium-Binding Proteins; D053331:Ectodysplasins; D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008562:Membrane Glycoproteins; D008840:Microfilament Proteins; D016328:NF-kappa B; D011743:Pyrimidines; D013449:Sulfonamides; D000068718:Rosuvastatin Calcium; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; C500593:Cybb protein, rat; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; C515768:Cyba protein, rat