Effects of 17beta-oestradiol on cerebral ischaemic damage and lipid peroxidation

• Published in: Brain research Vol. 1036; no. 1-2; p. 155
• Main Authors: Gordon, Kirsty B, Macrae, I Mhairi, Carswell, Hilary V O
• Format: Journal Article
• Language: English
• Published: Netherlands 02.03.2005
• Subjects: Aldehydes - metabolism; Animals; Antioxidants - adverse effects; Brain Ischemia - metabolism; Brain Ischemia - physiopathology; Cerebral Cortex - drug effects; Cerebral Cortex - pathology; Cerebral Cortex - physiopathology; Cerebral Infarction - chemically induced; Cerebral Infarction - metabolism; Cerebral Infarction - physiopathology; Disease Models, Animal; Disease Progression; Drug Implants; Estradiol - adverse effects; Estradiol - blood; Estradiol - pharmacology; Female; Infarction, Middle Cerebral Artery - metabolism; Infarction, Middle Cerebral Artery - physiopathology; Lipid Peroxidation - drug effects; Lipid Peroxidation - physiology; Nerve Degeneration - chemically induced; Nerve Degeneration - metabolism; Nerve Degeneration - physiopathology; Neurologic Examination; Ovariectomy; Oxidative Stress - drug effects; Oxidative Stress - physiology; Rats; Rats, Sprague-Dawley; Up-Regulation - drug effects; Up-Regulation - physiology
• ISSN: 0006-8993

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. 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. 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). 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.