ORIGIN OF ISCHEMIA-INDUCED GLUTAMATE EFFLUX IN THE CA1 FIELD OF THE GERBIL HIPPOCAMPUS - AN IN-VIVO BRAIN MICRODIALYSIS STUDY

In vivo brain microdialysis experiments were performed in the gerbil t o evaluate the origin of accumulation of extracellular glutamate under transient ischemia. Microdialysis probes were positioned in the CA1 f ield of the hippocampus in which proliferation of astrocytes, death of CA1 pyramidal neurons, and damage of presynaptic terminals had been i nduced by 5-min ischemia 10-14 days before the microdialysis experimen t; in the white matter of the cerebral cortex, which contained few neu rons, few presynaptic terminals, and many astrocytes; or in the histol ogically normal CA1 field of the hippocampus, and then 5- or 20-min is chemia was induced. When 5-min ischemia was induced, no significant in crease in glutamate content was observed in the CA1 field that showed proliferation of astrocytes, death of CA1 pyramidal neurons, and damag e of presynaptic terminals and in the white matter of the cerebral cor tex, whereas a significant increase in glutamate (15-fold) was observe d in the histologically normal CA1 field. When 20-min ischemia was ind uced, no significant increase in glutamate content was observed in the CA1 field that showed proliferation of astrocytes, death of CA1 pyram idal neurons, and damage of presynaptic terminals and in the white mat ter during the first 10 min after the onset of 20-min ischemia, but re markable ischemia-induced increases in glutamate were observed during the last 10 min of 20-min ischemia in both areas. An excessive increas e in glutamate (100-fold) was observed during 20-min ischemia in the n ormal CA1 field of the hippocampus. When a probe was positioned in the CA1 field of the hippocampus in which presynaptic terminals of Schaff er collaterals and commissural fibers had been eliminated by bilateral kainate injections into the lateral ventricles 4-7 days before the mi crodialysis experiment and then 5-min ischemia was induced, a signific ant increase in glutamate was observed during the last half of 5-min i schemia. These results suggest that the efflux of glutamate from astro cytes does not contribute to the large ischemia-induced glutamate accu mulation in the CA1 field of the hippocampus during 5-min ischemia but contributes to the ischemia-induced increase in glutamate level durin g ischemia with a longer duration and that ischemia-induced efflux of glutamate in the CA1 field during 5-min ischemia originates mainly fro m neuronal elements: presynaptic terminals and postsynaptic neurons.