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Hydrogen-rich water(HRW) has anti-oxidant activity and it exerts a neuroprotectiveeffects during ischemic brain injury.Calcium-buffering proteins includingparvalbumin and hippocalcin are involved in neuronal differentiation andmaturation through calcium signaling.This study investigated whether HRW moderates parvalbumin and hippocalcin expression in cerebralischemia and glutamate toxicity-induced neuronal cell death.Focal cerebralischemia was induced by middle cerebral artery occlusion (MCAO).MaleSprague-Dawley rats were treated with distilled water or HRW (6 ml/kg per rat)before and after MCAO, and cerebral cortical tissues were collected 1, 7 and 14 days after MCAO.Parvalbumin and hippocalcin levels were decreased in distilled water-treated animalwith MCAO, whereas HRW prevented the ischemic injury-inducedreduction in these proteins.In cultured hippocampal cells, glutamate toxicitydecreased parvalbumin and hippocalcin levels, while HRW treatmentprevented the glutamate exposure-induced diminished in these proteinslevels.HRW also attenuated the glutamate toxicity-induced increase inintracellular Ca2+levels.These results suggest that the maintenance ofparvalbumin and hippocalcin levels by HRW in ischemic injurycontributes to the neuroprotective effect of HRW against neuronal celldamage.