RELATIONSHIP BETWEEN EXTRACELLULAR NEUROTRANSMITTER AMINO-ACIDS AND ENERGY-METABOLISM DURING CEREBRAL-ISCHEMIA IN RATS MONITORED BY MICRODIALYSIS AND INVIVO MAGNETIC-RESONANCE SPECTROSCOPY

The time-course of changes in extracellular glutamate and energy metabolism during 30 or 60 min of complete cerebral ischemia and 60-90 min of reperfusion was investigated by microdialysis and magnetic resonance spectroscopy in parallel groups of rats. During the first 10 min of ischemia, adenosine triphosphate (ATP) was completely depleted, and lactate increased 10-fold; after 30 min, intracellular pH had decreased to 6.33 +/- 0.11. ATP and lactate did not change further between 30 and 60 min of ischemia. Glutamate increased 30-fold between 10 and 30 min of ischemia and continued to increase in the 60-min ischemia group. After 30 min of reperfusion, glutamate had returned to pre-ischemic levels in both groups. The cellular energy state recovered within 50-60 min after 30 min of ischemia but never returned to more than 60% of baseline values after 60 min of ischemia. The continued increase in extracellular glutamate after total depletion of ATP suggests that glutamate release during ischemia is not entirely energy dependent. Ca2+-independent glutamate release and failure of energy-dependent glutamate re-uptake mechanisms may result in continued increase in extracellular glutamate. The rapid normalization of extracellular glutamate after 30 and 60 min of ischemia despite differences in the recovery of energy metabolism suggests that the glutamate levels were reduced by an energy-independent mechanism, such as diffusion into the restored circulation.