ABSTRACT
An in vivo model of glutamate excitotoxicity in which glutamate is applied to the cortex of rats through a microdialysis probe has been used to investigate the neuroprotective processes initiated by 17β-estradiol. Rats were pre-treated with 17β-estradiol i.v. before local application of glutamate. The experimental results showed that pre-treatment with 17β-estradiol significantly reduced the size of the glutamate-induced lesion. In the microdialysates, the peak of lactate observed immediately after glutamate application was significantly higher and longer lasting after 17β-estradiol pre-treatment. The level of extracellular glucose was markedly decreased concomitantly to the increase in lactate, but no difference could be observed with and without 17β-estradiol pre-treatment. These suggest a new neuroprotective mechanism of 17β-estradiol by activating glutamate-induced lactate production. This effect on lactate production and lesion reduction is estrogen receptor dependent and is abolished totally by estrogen antagonist tamoxifen. It was also demonstrated here that high lactate subserves estrogen neuroprotection during glutamate toxicity.
ABSTRACT
An in vivo model of glutamate excitotoxicity in which glutamate is applied to the cortex of rats through a microdialysis probe has been used to investigate the neuroprotective processes initiated by 17β-estradiol. Rats were pre-treated with 17β-estradiol i.v. before local application of glutamate. The experimental results showed that pre-treatment with 17β-estradiol significantly reduced the size of the glutamate-induced lesion. In the microdialysates, the peak of lactate observed immediately after glutamate application was significantly higher and longer lasting after 17β-estradiol pre-treatment. The level of extracellular glucose was markedly decreased concomitantly to the increase in lactate, but no difference could be observed with and without 17β-estradiol pre-treatment. These suggest a new neuroprotective mechanism of 17β-estradiol by activating glutamate-induced lactate production. This effect on lactate production and lesion reduction is estrogen receptor dependent and is abolished totally by estrogen antagonist tamoxifen. It was also demonstrated here that high lactate subserves estrogen neuroprotection during glutamate toxicity.