CHANGES IN AMINO-ACID NEUROTRANSMITTERS AND CEREBRAL BLOOD-FLOW IN THE ISCHEMIC PENUMBRAL REGION FOLLOWING MIDDLE CEREBRAL-ARTERY OCCLUSIONIN THE RAT - CORRELATION WITH HISTOPATHOLOGY

We simultaneously measured neurotransmitter amino acids by the microdi alysis technique and cortical CBF by laser-Doppler flowmetry in the is chemic penumbral cortex of rats subjected to 2-h normothermic (36.5-37 .5-degrees-C) transient middle cerebral artery (MCA) clip-occlusion. B rains were perfusion-fixed 3 days later and infarct volume measured. C BF (% of preischemic values) fell to 32 +/- 2% (mean +/- SD) during is chemia and rose to 157 +/- 68% during recirculation. Extracellular glu tamate levels increased from a baseline value of 7 +/- 3 muM to a peak value of 180 +/- 247 muM 20-30 min following onset of ischemia but su bsequently returned to near baseline levels after 70 min of ischemia d espite ongoing MCA occlusion. The threshold CBF for moderate glutamate release was 48%. Massive glutamate release was seen during the first 60 min of MCA occlusion in the two animals showing the largest infarct s and occurred at CBF values less-than-or-equal-to 20% of control leve ls. Mean CBF during ischemia exhibited an inverse relationship with in farct volume, and the magnitude of glutamate release during ischemia w as positively correlated with infarct volume. Extracellular gamma-amin obutyrate and glycine changes were similar to those of glutamate but s howed no significant correlation with infarct volume. These results su ggest that (a) accumulation of extracellular glutamate is an important determinant of injury in the setting of reversible MCA occlusion and (b) reuptake systems for neurotransmitter amino acids may be functiona l in the penumbra during transient focal ischemia.