Effect of Hyperglycemia on Glutamate , Glycine and Aspartate Concentrations during Peri-ischemic Periods in the Rabbit Hippocampus

Choi, Kyu Taek

Abstract

Hyperglycemia has repeatedly been shown to exacerbate the neurologic injury produced by episodes of global cerebral ischemia. Under hypoxic conditions, glucose may be metabolized to glutamate, a known neurotoxin which has been implicated as a mediator of ischemic neumnal cell death. This study examined the effect of pre-existing hyperglycemia on the extracellular concentrations of glutamate and glycine in the rabbit hippocampus using in vivo microdialysis during brief episodes of transient global ischemia. Sixteen rabbits were anesthetized with halo- thane and mechanically ventilated with oxygen. Microdialysis probes were stereotacticly inserted into the dorsal hippocampus. Animals were randomized to receive an intravenous infusion of either saline or dextrose. The dextrose infusion rate was adjusted to produce a blood glucose level of approximately 40 mg/dl. Global cerebral ischemia (7.5 min duration) was then produced by the combination of neck tourniquet inflation and the induction of systemic hypotension. Dialystate was collected throughout the peri-ishemic period and analyzed by liquid chromato- graphy for glutamate, aspartate and glycine concentrations. There were no significant differences in physiologic variables among the groups with the exception of the intended increase in blood glucose concentrations in the dextrose-treated animals. Glutamate and glycine concentrations in the dialysate were similar between the three groups during the baseline period. Administration of dextmse had no effect on these levels. As anticipated, glutamate and glycine concentrations increased several fold during each of the ischemic periods when compared to baseline. However, hippocampal glutamate concentrations were lower in the dextrose treated groups during the peri-ischemic period (p=0,02). Glycine concentrations were higher during the reperfusion period in the dextrose-treated animals when compared with saline controls (p=0.03). Aspartate eoncentrations increased during the peri-ischemic period in the hyperglycemic group. However, there was not statistically significant. The results of this study suggest that hyperglycemia does not exert its detrimental effects by the enhanced release or production of glutamate. It may be that with this short duration of ischemia, pre-existing hyperglycemia is able to provide additional substrate for metabolism and cellular homeostasis thereby attenuating the synaptic release of glutamate. The increased concentration of extracellular glycine which was observed in the dextrose-treated animals may contribute to the neurologic injury which occurs during episodes of global ischemia.