title: Effects of 17beta-oestradiol on cerebral ischaemic damage and lipid peroxidation.
abstract: BACKGROUND
  Numerous studies demonstrate oestrogen's neuroprotective effect in stroke models, although the mechanisms are unclear. Since oestrogen is an antioxidant, we tested the hypothesis that oestrogen reduces stroke-induced damage by reducing free radical damage, particularly lipid peroxidation.
  
  
  METHODS
  Sprague-Dawley rats were ovariectomised and a 17beta-oestradiol (0.25 mg, 21 day release) or placebo pellet implanted subcutaneously. Two weeks later, permanent middle cerebral artery occlusion (MCAO) was induced by intraluminal filament. At 2 and 24 h post-MCAO, neurological deficits were assessed. At the 24 h end point, plasma oestradiol was measured and brain sections stained with haematoxylin and eosin or lipid peroxidation marker, 4-hydroxynonenol (4-HNE) immunohistochemistry carried out to measure infarct volume and volume of tissue displaying oxidative damage, respectively.
  
  
  RESULTS
  Plasma 17beta-oestradiol in oestradiol and placebo groups was 72.6+/-38.0 and 9.3+/-7.4 pg/ml (mean+/-SD), respectively. Infarct volume was significantly increased (118%) with oestradiol treatment (oestradiol=124+/-84.5, placebo=57+/-46.4 mm3, mean+/-SD, P<0.05). The relationship between 4-HNE and infarct volume was significantly influenced by 17beta-oestradiol. Neurological deficits were similar between groups (oestradiol median=13, placebo=14, max score=33).
  
  
  CONCLUSIONS
  Two week pre-treatment with a high physiological dose of 17beta-oestradiol increased infarct volume after permanent MCAO. Although contrary to our original hypothesis, this result demonstrates that oestrogen does have the capacity to promote detrimental actions in the stroke-injured brain. Given the wide use of oestrogen (contraception, osteoporosis and menopause), more research to clarify the influence of oestrogen on brain injury is urgently required.
authors.affiliation: Division of Clinical Neuroscience, Wellcome Surgical Institute, University of Glasgow, Garscube Estate, Bearsden Road, Glasgow G61 1QH, UK.
authors.forename: Kirsty B
authors.initials: KB
authors.lastname: Gordon
authors.forename: I Mhairi
authors.initials: IM
authors.lastname: Macrae
authors.forename: Hilary V O
authors.initials: HV
authors.lastname: Carswell
mesh_terms: D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000009:adverse effects; D002545:Brain Ischemia / Q000378:metabolism* / Q000503:physiopathology; D002540:Cerebral Cortex / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D002544:Cerebral Infarction / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D018450:Disease Progression; D004343:Drug Implants; D004958:Estradiol / Q000009:adverse effects* / Q000097:blood / Q000494:pharmacology; D005260:Female; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism / Q000503:physiopathology; D015227:Lipid Peroxidation / Q000187:drug effects* / Q000502:physiology; D009410:Nerve Degeneration / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D009460:Neurologic Examination; D010052:Ovariectomy; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
chemical_list: D000447:Aldehydes; D000975:Antioxidants; D004343:Drug Implants; D004958:Estradiol; C027576:4-hydroxy-2-nonenal