Cellular Metabolism and Neuronal Injury

Hypoglycemia is part of the ischemic cascade and can result in neurodegeneration in both in vitro and in vivo models. Neuronal cells in hypoxic environments may experience loss of aerobic as well as anaerobic metabolism. This loss of metabolism has been suggested to mediate neuronal death during ischemia independent of the loss of calcium homeostasis. During periods of focal ischemia, patches of hypermetabolism surrounding the ischemic core are known to occur. It has not been established whether this hypermetabolism prolongs survival or promotes cell death. Recently, glucose has been shown to increase calcium current through dihydropyridine-sensitive calcium channels in pancreatic cells or through NMDA channels in cortical cells. Yet, in PC-12 cells, a four fold elevation above physiologic glucose levels reduced the dihydropyridine-sensitive, depolarization-induced increase in calcium, suggesting a neuroprotective effect with increased metabolism. We are actively investigating the role of cellular glucose metabolism during neuronal injury.