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 exact mechanism of which is unknown. Lactic acidosis has been implicated; however, increases in the excitotoxic amino acid glutamate, which correlate with increased neuronal damage, may be the cause for the increased damage seen 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-vessel occlusion model, global ischemia was assessed at 5 to 7 days after treatment 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 collect superfusates under basal, ischemic, and reperfusion conditions and analyzed for nine different amino acids using high-performance liquid chromatography. RESULTS: Plasma glucose levels were significantly higher in the acute and chronic 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 reduced during reperfusion in the acute STZ group and during ischemia/reperfusion in the chronic STZ group as compared with the controls. Levels of extracellular gamma -aminobutyric acid were significantly reduced in the acute and chronic STZ groups as compared with the controls. CONCLUSION: A chronic state of hyperglycemia results in reduction in extracellular brain glutamate levels during ischemia/reperfusion and therefore does not appear to be responsible for the increased neuronal damage seen in diabetic stroke. Chronic hyperglycemia also causes decreased extracellular gamma -aminobutyric acid levels, which, because of the loss of the inhibitory effects of this neurotransmitter, could contribute to the increased damage observed in hyperglycemic stroke.