Neuroprotective effect of high glucose against NMDA, free radical, and oxygen-glucose deprivation through enhanced mitochondrial potentials

Cultured cortical neurons maintained in 25 mM glucose underwent a widesprea d neuronal death after exposure to NMDA, AMPA, and kainate. Among these, NM DA toxicity was substantially reduced in neurons maintained in 100 mM gluco se. NMDA-induced increase in [Ca2+](i) and reactive oxygen species was atte nuated in neurons maintained in high glucose that revealed increased mitoch ondrial membrane and redox potentials as determined using rhodamine 123 and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide. p-trifluoro methoxyphenylhydrazone, KCN, and rotenone, the selective inhibitors of mito chondrial potential, abrogated neuroprotective effect of high glucose again st NMDA. The neuroprotective action of high glucose was extended against ox ygen or combined oxygen-glucose deprivation. The present study provides evi dence that prolonged exposure of cortical cells to high glucose attenuates NMDA- and free radical-mediated neuronal death via enhanced mitochondrial f unction.