The effect of streptozotocin-induced diabetes on the release of excitotoxic and other amino acids from the ischemic rat cerebral cortex

OBJECTIVE: Hyperglycemic stroke results in increased neuronal damage, the e xact mechanism of which is unknown. Lactic acidosis has been implicated; ho wever, increases in the excitotoxic amino acid glutamate, which correlate w ith increased neuronal damage, may be the cause for the increased damage se en in hyperglycemic stroke. METHODS: Ten Sprague-Dawley rats were treated with streptozotocin (STZ; 50 mg/kg), and 12 normoglycemic rats were used as controls. Using a four-vesse l occlusion model, global ischemia was assessed at 5 to 7 days after treatm ent in five animals (acute STZ group) or at 4 to 6 weeks after treatment in five animals (chronic STZ group). The cortical cup model was used to colle ct superfusates under basal, ischemic, and reperfusion conditions and analy zed for nine different amino acids using high-performance liquid chromatogr aphy. RESULTS: Plasma glucose levels were significantly higher in the acute and c hronic STZ groups as compared with the control group. Plasma lactate levels were higher in the acute STZ group as compared with the control or chronic STZ groups. Extracellular cortical glutamate levels were significantly red uced during reperfusion in the acute STZ group and during ischemia/reperfus ion in the chronic STZ group as compared with the controls. Levels of extra cellular gamma -aminobutyric acid were significantly reduced in the acute a nd chronic STZ groups as compared with the controls. CONCLUSION: A chronic state of hyperglycemia results in reduction in extrac ellular brain glutamate levels during ischemia/reperfusion and therefore do es not appear to be responsible for the increased neuronal damage seen in d iabetic stroke. Chronic hyperglycemia also causes decreased extracellular g amma -aminobutyric acid levels, which, because of the loss of the inhibitor y effects of this neurotransmitter, could contribute to the increased damag e observed in hyperglycemic stroke.