Neuroprotection by estrogens in a mouse model of focal cerebral ischemia and in cultured neurons: Evidence for a receptor-independent antioxidative mechanism

Estrogens have been suggested for the treatment of neurodegenerative disord ers, including stroke, because of their neuroprotective activities against various neurotoxic stimuli such as glutamate, glucose deprivation, iron, or beta-amyloid. Here, the authors report that 17 beta-estradiol (0.3 to 30 m g/kg) and 2-OH-estradiol (0.003 to 30 mg/kg) reduced brain tissue damage af ter permanent occlusion of the middle cerebral artery in male NMRI mice. In vitro, 17 beta-estradiol (1 to 10 mu mol/L) and 2-OH-estradiol (0.01 to 1 mu mol/L) reduced the percentage of damaged chick embryonic neurons treated with FeSO4. In these primary neurons exposed to FeSO4, the authors also fo und reactive oxygen species to be diminished after treatment with 17 beta-e stradiol (1 to 10 mu mol/L) or 2-OH-estradiol (0.01 to 10 mu mol/L), sugges ting a strong antioxidant. activity of the estrogens that were used. Neithe r the neuroprotective effect nor the free radical scavenging properties of the estrogens were influenced by the estrogen receptor antagonist tamoxifen . The authors conclude that estrogens protect neurons against damage by rad ical scavenging rather than through estrogen receptor activation.