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

Brain Res. 2005 Mar 2;1036(1-2):155-62. doi: 10.1016/j.brainres.2004.12.052.


Introduction: 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).

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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


  • Aldehydes
  • Antioxidants
  • Drug Implants
  • Estradiol
  • 4-hydroxy-2-nonenal