Characterization of transient focal ischemia-induced increases in extracellular glutamate and aspartate in spontaneously hypertensive rats

Using middle cerebral artery occlusion (MCAO) and in vivo microdialysis, we have evaluated the changes in extracellular concentrations of the excitato ry amino acids (EAA) glutamate and aspartate during varying periods of MCAO (0, 30, 60 min) in the striatum of spontaneously hypertensive rats (SHR). A positive correlation between occlusion time-dependent elevations in EAAs and the resulting ischemic injury was observed, This is the first demonstra tion of the temporal profile of EAA efflux during transient focal ischemia in SHRs, Possible sources and mechanisms of ischemia-induced EAA efflux wer e examined during 60 min of MCAO. Removal of Ca2+ from the microdialysis in fusion media significantly attenuated ischemia-induced increases in both gl utamate (from ischemic peak of 4892 +/- 1298 to 1144 +/- 666% of preischemi c values) and aspartate (from 2703 +/- 682 to 2090 +/- 599% of preischemic values). Similarly, infusion of the voltage dependent Na+ channel blocker t etrodotoxin (TTX; 10 muM) significantly attenuated MCAO-induced increases i n glutamate (to 1313 a 648%) and aspartate (to 359 +/- 114%), Infusion of t he GLT-1 selective nontransportable inhibitor, dihydrokainate (DHK; 1mM) al so significantly attenuated the ischemia-induced increases in both EAAs (12 85 +/- 508 and 1366 +/- 741% of the preischemic levels, respectively). Thes e results indicate that during transient focal ischemia the increase in ext racellular EAAs originates from both the neuronal pool, via conventional ex ocytotic release, and glial sources via the reversal of the GLT-1 transport er. (C) 2001 Elsevier Science Inc.