Abstract

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 [Ca²⁺]_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.