Summary
Anin 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 17ß-estradiol. Rats were pre-treated with 17ß-estradiol i. v. before local application of glutamate. The experimental results showed that pre-treatment with 17ß-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 17ß-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 17ß-estradiol pre-treatment. These suggest a new neuroprotective mechanism of 17ß-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.
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This project was supported by grants from the Novartis Foundation and the department of Surgery, University Hospital Basel, Switzerland.
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Jincao, C., Ting, L., Ritz, M.F. et al. Effect of 17β-estradiol on the brain damage and metabolic changes in rats. Current Medical Science 21, 62–64 (2001). https://doi.org/10.1007/BF02888040
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DOI: https://doi.org/10.1007/BF02888040