A. Mendelowitsch et al., 17 beta-Estradiol reduces cortical lesion size in the glutamate excitotoxicity model by enhancing extracellular lactate: a new neuroprotective pathway, BRAIN RES, 901(1-2), 2001, pp. 230-236
Estrogens play an important role in neuronal function and in protecting neu
rones in the cerebral cortex against pathological conditions, An in vivo mo
del of glutamate excitotoxicity in which glutamate is applied to the cortex
of rats through a microdialysis probe has been used to investigate the neu
roprotective processes initiated by 17 beta -estradiol. Rats were pre-treat
ed with 17 beta -estradiol (i.v.) before local application of 100 mM glutam
ate into the cortex through a microdialysis probe. Pre-treatment with 17 be
ta -estradiol significantly reduced the size of the glutamate-induced corti
cal lesion. In the cortical microdialysates collected from the probe, a pea
k of lactate was observed immediately after glutamare application. After 17
beta -estradiol pre-treatment this peak of lactate was significantly highe
r with estradiol than without 120 min after glutamate application, reaching
700% basal level at the end of measurement. The level of extracellular glu
cose was markedly decreased with and without 17 beta -estradiol pre-treatme
nt. Local blockage of neuronal lactate transporters with alpha -cyano-4-hyd
roxycinnamate (4-CIN) completely abolished the neuroprotective effect of 17
beta -estradiol and induced a larger cortical lesion. An accumulation of e
xtracellular lactate was observed after inhibition of the lactate transport
ers suggesting that transport of lactate into neurones is necessary for the
neuroprotective effect of 17 beta -estradiol. The anti-estrogen tamoxifen
also abolished the neuroprotective effect of 17 beta -estradiol on the lesi
on size and inhibited the production of lactate. These results suggest a ne
w neuroprotective mechanism of 17 beta -estradiol by activating glutamate-s
timulated lactate production, which is estrogen receptor-dependent. (C) 200
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