EFFECT OF HYPERGLYCEMIA ON PERI-ISCHEMIC NEUROTRANSMITTER LEVELS IN THE RABBIT HIPPOCAMPUS

This study examined the effect of preexisting hyperglycemia on the extracellular concentrations of glutamate and glycine in the rabbit hippocampus using in vivo microdialysis during brief episodes of transient global ischemia. 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 neuronal cell death. In this study, microdialysis probes were stereotacticly inserted into the dorsal hippocampus of anesthetized rabbits. Animals were randomized to receive an i.v. infusion of either saline or dextrose. Global cerebral ischemia was then produced by the combination of neck tourniquet inflation and the induction of systemic hypotension. Administration of dextrose had no effect on these basal levels of glutamate or glycine. During ischemia, glutamate and glycine concentrations increased several-fold when compared with 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). 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. The results of this study suggest that hyperglycemia does not exert its detrimental effects by increasing the extracellular concentration of glutamate.