title: Continuous oral administration of atorvastatin ameliorates brain damage after transient focal ischemia in rats.
abstract: OBJECTIVE
  Pre-treatment with statins is known to ameliorate ischemic brain damage after experimental stroke, and is independent of cholesterol levels. We undertook pre- vs post-ischemic treatment with atorvastatin after focal cerebral ischemia in rats.
  
  
  METHODS
  Male Sprague-Dawley rats underwent transient 90-min middle cerebral artery occlusion (MCAO). Atorvastatin (20mg/kg/day) or vehicle was administered orally. Rats were divided into vehicle-treated, atorvastatin pre-treatment, atorvastatin post-treatment, and atorvastatin continuous-treatment groups. In the pre-treatment, rats were given atorvastatin or vehicle for 7 days before MCAO. In the post-treatment, rats received atorvastatin or vehicle for 7 days after MCAO. Measurement of infarct volume, as well as neurological and immunohistochemical assessments, were done 24h and 7 days after reperfusion.
  
  
  RESULTS
  Each atorvastatin-treated group demonstrated significant reductions in infarct and edema volumes compared with the vehicle-treated group 24h after reperfusion. Seven days after reperfusion, infarct volumes in the post-treatment group and continuous-treatment group (but not the pre-treatment group) were significantly smaller than in the vehicle-treated group. Only the continuous-treatment group had significantly improved neurological scores 7 days after reperfusion compared with the vehicle group. Post-treatment and continuous-treatment groups had significantly decreased lipid peroxidation, oxidative DNA damage, microglial activation, expression of tumor necrosis factor-alpha, and neuronal damage in the cortical ischemic boundary area after 7 days of reperfusion.
  
  
  CONCLUSIONS
  These results suggest that continuous oral administration (avoiding withdrawal) with statins after stroke may reduce the extent of post-ischemic brain damage and improve neurological outcome by inhibiting oxidative stress and inflammatory responses.
authors: Department of Neurological Science, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan.
authors: Tomonari
authors: T
authors: Saito
authors: Department of Neurological Science, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan. Electronic address: cnito@nms.ac.jp.
authors: Chikako
authors: C
authors: Nito
authors: Department of Neurological Science, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan.
authors: Masayuki
authors: M
authors: Ueda
authors: Department of Neurological Science, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan.
authors: Toshiki
authors: T
authors: Inaba
authors: Department of Neurological Science, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan.
authors: Fumio
authors: F
authors: Kamiya
authors: Department of Neurological Science, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan.
authors: Kanako
authors: K
authors: Muraga
authors: Department of Neurological Science, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan.
authors: Ken-Ichiro
authors: K
authors: Katsura
authors: Department of Neurological Science, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan.
authors: Yasuo
authors: Y
authors: Katayama
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000069059:Atorvastatin; D001921:Brain / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D001929:Brain Edema / Q000209:etiology / Q000473:pathology; D002545:Brain Ischemia / Q000150:complications / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D004249:DNA Damage / Q000187:drug effects; D006538:Heptanoic Acids / Q000008:administration & dosage / Q000627:therapeutic use*; D015227:Lipid Peroxidation / Q000187:drug effects; D008279:Magnetic Resonance Imaging; D008297:Male; D017628:Microglia / Q000187:drug effects / Q000473:pathology; D059906:Neuroimaging; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects; D011758:Pyrroles / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D006538:Heptanoic Acids; D018696:Neuroprotective Agents; D011758:Pyrroles; D014409:Tumor Necrosis Factor-alpha; D000069059:Atorvastatin
keywords: Atorvastatin; Focal cerebral ischemia; Inflammation; Neuroprotection; Oxidative stress