title: Rosuvastatin ameliorates early brain injury after subarachnoid hemorrhage via suppression of superoxide formation and nuclear factor-kappa B activation in rats.
abstract: BACKGROUND
  Statins, or 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, have been suggested to possess pleiotropic effects, including antioxidant and anti-inflammatory properties. We investigated the protective effects of pretreatment with rosuvastatin, a relatively hydrophilic statin, on early brain injury (EBI) after a subarachnoid hemorrhage (SAH), using the endovascular perforation SAH model.
  
  
  METHODS
  Eighty-six male Sprague-Dawley rats were randomly divided into 3 groups: (1) sham operation, (2) SAH+vehicle, and (3) SAH+10 mg/kg rosuvastatin. Rosuvastatin or vehicle was orally administered to rats once daily from 7 days before to 1 day after the SAH operation. After SAH, we examined the effects of rosuvastatin on the neurologic score, brain water content, neuronal cell death estimated by terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate nick end labeling staining, blood-brain barrier disruption by immunoglobulin G (IgG) extravasation, oxidative stress, and proinflammatory molecules.
  
  
  RESULTS
  Compared with the vehicle group, rosuvastatin significantly improved the neurologic score and reduced the brain water content, neuronal cell death, and IgG extravasation. Rosuvastatin inhibited brain superoxide production, nuclear factor-kappa B (NF-κB) activation, and the increase in activated microglial cells after SAH. The increased expressions of tumor necrosis factor-alpha, endothelial matrix metalloproteinase-9, and neuronal cyclooxygenase-2 induced by SAH were prevented by rosuvastatin pretreatment.
  
  
  CONCLUSIONS
  The present study demonstrates that rosuvastatin pretreatment ameliorates EBI after SAH through the attenuation of oxidative stress and NF-κB-mediated inflammation.
authors: Department of Pharmacology and Molecular Therapeutics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors: Ken
authors: K
authors: Uekawa
authors: Department of Pharmacology and Molecular Therapeutics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors: Yu
authors: Y
authors: Hasegawa
authors: Department of Pharmacology and Molecular Therapeutics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors: Mingjie
authors: M
authors: Ma
authors: Department of Pharmacology and Molecular Therapeutics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors: Takashi
authors: T
authors: Nakagawa
authors: Department of Pharmacology and Molecular Therapeutics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors: Tetsuji
authors: T
authors: Katayama
authors: Department of Pharmacology and Molecular Therapeutics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors: Daisuke
authors: D
authors: Sueta
authors: Department of Pharmacology and Molecular Therapeutics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors: Kensuke
authors: K
authors: Toyama
authors: Department of Pharmacology and Molecular Therapeutics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors: Keiichiro
authors: K
authors: Kataoka
authors: Department of Pharmacology and Molecular Therapeutics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors: Nobutaka
authors: N
authors: Koibuchi
authors: Department of Neurosurgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors: Takayuki
authors: T
authors: Kawano
authors: Department of Neurosurgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors: Jun-ichi
authors: J
authors: Kuratsu
authors: Department of Pharmacology and Molecular Therapeutics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan. Electronic address: kimmitsu@gpo.kumamoto-u.ac.jp.
authors: Shokei
authors: S
authors: Kim-Mitsuyama
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D001930:Brain Injuries / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D005464:Fluorobenzenes / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects; D011743:Pyrimidines / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000068718:Rosuvastatin Calcium; D013345:Subarachnoid Hemorrhage / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology / Q000627:therapeutic use*; D013481:Superoxides / Q000378:metabolism*
chemical_list: D005464:Fluorobenzenes; D016328:NF-kappa B; D018696:Neuroprotective Agents; D011743:Pyrimidines; D013449:Sulfonamides; D013481:Superoxides; D000068718:Rosuvastatin Calcium
keywords: Subarachnoid hemorrhage; early brain injury; nuclear factor-kappa B; reactive oxygen species; rosuvastatin