Further studies on the effects of topical lactate on amino acid efflux from the ischemic rat cortex

A rat four-vessel cerebral occlusion model was used to examine the effects of D-lactate and oxamate, a lactate dehydrogenase inhibitor, on cortical wi ndow superfusate levels of amino acids, glucose and L-lactate. Superfusate levels of aspartate, glutamate, taurine, GABA and phosphoethanolamine rose during ischemia and then declined during reperfusion. Glycine and alanine l evels tended to increase during reperfusion, whereas glutamine levels were lower. Serine levels were not altered. Glucose levels declined rapidly duri ng ischemia and recovered during reperfusion. Lactate levels were sustained during ischemia and increased during reperfusion. Unlike L-lactate, which attenuated ischemia/reperfusion (I/R) evoked amino acid release (J.W. Phill is, D. Song, L.L. Guyot, M.H. O'Regan, Lactate reduces amino acid release a nd fuels recovery of function in the ischemic brain. Neurosci. Lett. 272 (1 999) 195-198). topical application of D-lactate (20 mM), which is not used as an energy substrate, enhanced the I/R release of aspartate, glutamate, G ABA and taurine into cortical superfusates. and also elevated L-lactate lev els above those in the controls. Glucose levels were not altered. Oxamate ( 20 mM) application elevated the pre-ischemia levels of alanine, glycine and GABA and those of GABA during ischemia. Levels of all amino acids, with th e exception of phosphoethanolamine, were elevated during reperfusion. Oxama te, an inhibitor of lactate dehydrogenases 1 and 5. did not alter the patte rn of efflux of glucose and L-lactate. In the presence of oxamate, L-lactat e (20 mM) failed to inhibit amino acid release. The failure of D-lactate to attenuate amino acid release confirms the inability of this isomer to act as a metabolic substrate. The oxamate data indicate that inhibition of lact ate dehydrogenase is detrimental to the viability of cortical cells during I/R, even though extracellular lactate levels are elevated. The pre-ischemi a increases in alanine and glycine are suggestive of elevations in pyruvate as a result of the block of its conversion to lactate, with transamination reactions converting pyruvate to form these amino acids. In summary, the r esults further substantiate the concept of a role for L-lactate as a cerebr al energy substrate. (C) 2001 Elsevier Science B.V. All rights reserved.