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 widespread neuronal death after exposure to NMDA, AMPA, and kainate. Among these, NMDA toxicity was substantially reduced in neurons maintained in 100 mM glucose. NMDA-induced increase in [Ca(2+)](i) and reactive oxygen species was attenuated in neurons maintained in high glucose that revealed increased mitochondrial membrane and redox potentials as determined using rhodamine 123 and 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide. p-trifluoromethoxy-phenylhydrazone, KCN, and rotenone, the selective inhibitors of mitochondrial potential, abrogated neuroprotective effect of high glucose against NMDA. The neuroprotective action of high glucose was extended against oxygen or combined oxygen-glucose deprivation. The present study provides evidence that prolonged exposure of cortical cells to high glucose attenuates NMDA- and free radical-mediated neuronal death via enhanced mitochondrial function.