EARLY CELLULAR SWELLING DURING CEREBRAL-ISCHEMIA INVIVO IS MEDIATED BY EXCITATORY AMINO-ACIDS RELEASED FROM NERVE-TERMINALS

This study demonstrates ischemic cellular swelling in vivo detected as changes in the concentration of C-14-sucrose pre-perfused into the extracellular space (ECS) as an ECS marker. Microdialysis was utilized as a means of perfusion and measurement of the extracellular concentration of C-14 sucrose ([C-14-sucrose]e). Concomitant with an abrupt increase in [K+]e at 1-3 min following the ischemia induction, [C-14-sucrose]e was also rapidly elevated. Since sucrose is not taken up by either cells or capillaries, the absolute amount of C-14-sucrose in the ECS must be unchanged. The increase therefore appears to represent a relative decrease in water volume in the ECS resulting from a movement of water into the cells, i.e. cellular swelling. Ca2+-free perfusate containing Co2+, which has been shown to block excitatory amino acid release during cerebral ischemia, significantly delayed the increase in [C-14-sucrose]e and [K+]e. Kynurenic acid, a broad-spectrum antagonist of excitatory amino acids, administered in situ through the dialysis probe also significantly delayed the increase in [C-14-sucrose]e and [K+]e. These findings indicate that the early cellular swelling occurring during cerebral ischemia is a result of massive ionic fluxes mediated by excitatory amino acids which are released by a Ca2+-dependent exocytotic process from the nerve terminals.