Inhibition of the early phase of free fatty liberation during cerebral ischemia by excitatory amino acid antagonist administered

Abstract

In order to ditermine the role of excitatory amino acids (EAAs) in free fatty acid (FFA) liberation during cerebral ischemia, we examined the effect on in situ adminstration of kynurenic acid, a broad-spectrum antagonist of EAA receptors, by microdialysis on the increase in FFA levels during ischemia in the rat hippocampus. A transient rapid increase in FFA levels, superimposed on a continued slow increase, was observed beginning at 1–2 min after ischemia induction. The early phase of FFA liberation. Development of massive ionic shifts during cerebral ischemia can be delayed for several minutes by kynurenic acid administered by the same procedure, suggesting a vital role for EAAs in the early appearance of anaxonic depolarization. The observed inhibition of early FFA liberation may thus be attributable to thedelay in development of massive ionic shifts and resulatant neurotransmitter release which may activate phospholipase A 2and C.