ALTERATIONS IN K-ACIDS AFTER FOCAL ISCHEMIA-REPERFUSION( EVOKED PROFILES OF NEUROTRANSMITTER AND NEUROMODULATOR AMINO)

Secondary elevations in extracellular amino acids occur during reperfu sion after transient cerebral ischemia. The delayed accumulation of ex citatory amino acids may contribute to the progressive development of neuronal injury. In this study, we explored the mechanisms that may be involved in this phenomenon. Microdialysis samples from probes locate d in rabbit cortex were analysed with a chiral amino acid procedure. C oncentrations of neurotransmitters (L-Glu, GABA), N-methyl-D-aspartate receptor modulators (D-Ser, Gly), an inhibitory neuromodulator (Tau), the lipid component phosphoethanolamine, and L-Gln, L-Ser and L-Ala w ere measured. Depolarization via perfusion with potassium was used to assess the status of release/reuptake systems at 2 and 4 h reperfusion after 2 h transient focal ischemia. Background experiments classified potassium evoked responses as calcium dependent or calcium-independen t by inclusion of 30 mu M omega-conopeptide MVIIC or by inclusion of 2 0 mM magnesium and ommision of calcium. During ischemia, large elevati ons of almost all amino acids occurred. During reperfusion, secondary elevations in transmitter amino acids (L-Glu, GABA) and N-methyl-D-asp artate receptor modulators (D-Ser, Gly) occurred. Tau remained slightl y elevated whereas the lipid component phosphoethanolamine remained hi gh and stable during reperfusion. Reperfusion significantly potentiate d the potassium response for amino acids with calcium-dependent respon ses (L-Glu and GABA). In contrast, calcium-independent responses (Tau, phosphoethanolamine, L-Gln) were significantly attenuated. Intermedia te behavior was observed with Gly, while no potassium responses were o bserved for D-Ser, L-Ser or L-Ala. These data demonstrate that perturb ations in evoked amino acid profiles after ischemia-reperfusion are se lective. Reduction of calcium-independent responses implicate a genera l decline in efficacy of transporter mechanisms that restore transmemb rane gradients of ions and transmitters. Decreased efficacy of transpo rter systems may reduce transmitter reuptake and account for the ampli fied release of L-Glu and GABA, thus contributing to progressive neura l dysfunction after cerebral ischemia. (C) 1997 IBRO. Published by Els evier Science Ltd.