Estradiol ameliorates the reduction in parvalbumin expression induced by ischemic brain injury

Estradiol plays a neuroprotective role against focal cerebral ischemia. Parvalbumin is an intracellular Ca(2+)-binding protein. It exerts a neuroprotective effect against cytotoxic Ca(2+) overload. This study investigated whether estradiol modulates parvalbumin expression in focal cerebral ischemia and glutamate-induced neuronal cell death. Adult female rats were ovariectomied and treated with vehicle or estradiol prior to middle cerebral artery occlusion (MCAO). The cerebral cortex was collected 24h after MCAO. A proteomics approach showed a decrease of parvalbumin in MCAO-operated animals, while estradiol prevented the MCAO-induced decrease in parvalbumin. Reverse transcription-PCR and Western blot analyses confirmed that estradiol treatment attenuated the MCAO-induced decrease in parvalbumin levels. The results of immunohistochemical staining showed that the number of parvalbumin-positive cells decreased in MCAO-operated animals, and estradiol prevented the MCAO-induced decrease in parvalbumin-positive cells. In cultured hippocampal cells, glutamate exposure raised the intracellular Ca(2+) concentration, while estradiol treatment attenuated this increase. Moreover, estradiol prevented the decrease in parvalbumin induced by glutamate toxicity. These findings suggest that estradiol exerts a neuroprotective effect by preventing the MCAO-induced decrease of parvalbumin and by regulating intracellular Ca(2+) levels.