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

• Published in: Brain research Vol. 1036; no. 1; pp. 155 - 162
• Main Authors: Gordon, Kirsty B., Macrae, I. Mhairi, Carswell, Hilary V.O.
• Format: Journal Article
• Language: English
• Published: London Elsevier B.V 02.03.2005; Amsterdam Elsevier; New York, NY
• Subjects: 4-Hydroxynonenol; Biological and medical sciences; Intraluminal thread; Medical sciences; Middle cerebral artery occlusion; Neurological assessment; Neurology; Oestrogen; Oxidative damage; Vascular diseases and vascular malformations of the nervous system; Ischaemia; Disorders of the nervous system; Oestrogen; Neurological assessment; Oxidative damage; Middle cerebral artery occlusion; 4-Hydroxynonenol; Intraluminal thread; Rat; Rodentia; Central nervous system; Estrogen; 17β-Estradiol; Cardiovascular disease; Lipids; Ovarian hormone; Encephalon; Vertebrata; Experimental disease; Mammalia; Ischemia; Animal; Sex steroid hormone; Peroxidation
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2004.12.052

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 17β-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 17β-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 mm 3, mean ± SD, P < 0.05). The relationship between 4-HNE and infarct volume was significantly influenced by 17β-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 17β-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.