ELEVATION OF NEUROACTIVE SUBSTANCES IN THE CORTEX OF CATS DURING PROLONGED FOCAL ISCHEMIA

Sustained accumulation of excitatory amino acids and other neuroactive substances may contribute to the delayed progression of infarction in focal ischemia. Following occlusion of the left middle cerebral arter y (MCAO), extracellular amino acid and purine catabolite concentration s as well as local CBF were repeatedly monitored for up to 15 h in aud itory (A) and somatosensory (SF) cortices of seven halothane-anestheti zed cats using microdialysis/HPLC and hydrogen clearance. MCAO resulte d in persistent reduction of local CBF, which was more severe in A (n = 6) than in SF (n = 6). Accordingly, higher transmitter amino acid an d purine catabolite concentrations were found in A than in SF during i schemia. Aspartate, glutamate, and gamma-aminobutyrate (GABA) as well as hypoxanthine and inosine reached maximum levels 1-2 h after onset o f ischemia (15-, 7-, 31 -, 8-, and 14-fold increases, respectively). M aximum levels remained almost constant, with the exception of inosine, which decreased subsequently. Glycine seemed to increase with prolong ed ischemia and reached maximum levels (10-fold) 15 h after occlusion. Adenosine peaked 30 min after occlusion (54-fold) and decreased there after to control levels within 1-2 h. One hour after occlusion, CBF th resholds for amino acid elevation were lower (glutamate and GABA appro ximately 20 ml 100 g-1 min-1 and glycine approximately 10 ml 100 g-1 m in-1) than 6 and 15 h after occlusion (thresholds for all amino acids at approximately 30 ml 100 g-1 min-1). These results indicate that in prolonged ischemia, excitotoxicity is an important factor, particularl y in border zones of ischemic foci. It may be enhanced by an increase of glycine and the early disappearance of adenosine, which are conside red to facilitate and inhibit, respectively, the deleterious effects o f excitatory amino acids.