Studies on the effects of lactate transport inhibition, pyruvate, glucose and glutamine on amino acid, lactate and glucose release from the ischemic rat cerebral cortex

A rat four vessel occlusion model was utilized to examine the effects of is chemia/reperfusion on cortical window superfusate. levels of amino acids, g lucose, and lactate. Superfusate aspartate, glutamate, phosphoethanolamine, taurine, and GABA were significantly elevated by cerebral ischemia, then d eclined during reperfusion. Other amino acids were affected to a lesser deg ree. Superfusate lactate rose slightly during the initial ischemic period, declined during continued cerebral ischemia and then was greatly elevated d uring reperfusion. Superfusate glucose levels declined to near zero levels during ischemia and then rebounded beyond basal levels during the reperfusi on period. Inhibition of neuronal lactate uptake with alpha -cyano-4-hydrox ycinnamate dramatically elevated superfusate lactate levels, enhanced the i schemia/reperfusion evoked release of aspartate but reduced glutamine level s. Topical application of an alternative metabolic fuel, glutamine, had a d ose dependent effect. Glutamine (1 mM) elevated basal superfusate glucose l evels, diminished the decline in glucose during ischemia, and accelerated i ts recovery during reperfusion, Lactate levels were elevated during ischemi a and reperfusion. These effects were not evident at 5 mM glutamine. At bot h concentrations, glutamine significantly elevated the superfusate levels o f glutamate. Topical application of sodium pyruvate (20 mM) significantly a ttenuated the decline in superfusate glucose during ischemia and enhanced t he levels of both glucose and lactate during reperfusion. However, it had l ittle effect on the ischemia-evoked accumulation of amino acids. Topical ap plication of glucose (450 mg/dL) significantly elevated basal superfusate l evels of lactate, which continued to be elevated during both ischemia and r eperfusion. The ischemia-evoked accumulations of aspartate, glutamate, taur ine and GABA were all significantly depressed by glucose, while phosphoetha nolamine levels were elevated. These results support the role of lactate in neuronal metabolism during ischemia/reperfusion. Both glucose and glutamin e were also used as energy substrates. In contrast, sodium pyruvate does no t appear to be as effectively utilized by the ischemic/reperfused rat brain since it did not reduce ischemia-evoked amino acid efflux.