Concentrations of glutamate released following spinal cord injury kill oligodendrocytes in the spinal cord

We investigated in vivo in rats whether sufficient glutamate is released following spinal cord injury (SCI) to kill oligodendrocytes. Microdialysis sampling was used to establish the level of glutamate released (550 +/- 80 (muM) in the white matter during SCI. This glutamate concentration was administered into the spinal cords of other rats and the densities of oligodendrocytes remaining 24 and 72 h later determined by counting cells immunostained with the oligodendrocyte marker CC-1. Administration of ACSF, 4.0 mM glutamate (estimated resulting tissue exposure 500 muM) and 10.0 mM glutamate by microdialysis reduced oligodendrocyte density 22%, 57%, and 74%, respectively, relative to normal at 24 h post-exposure. Therefore, sufficient glutamate is released following SCI to damage white matter. Oligodendrocyte densities near the fiber track were not significantly different at 72 h from 24 h post-exposure, so most glutamate-induced oligodendrocyte death occurs within 24 h after exposure. Injecting the AMPA/kainate receptor blocker NBQX into the spinal cord during glutamate administration reduced the glutamate-induced decrease in oligodendrocyte density, evidence for AMPA/kainate receptor involvement in glutamate-induced oligodendrocyte death. This work directly demonstrates in vivo that following SCI glutamate reaches concentrations toxic to white matter and that AMPA/kainate receptors mediate this glutamate toxicity to oligodendrocytes. (C) 2004 Elsevier Inc. All rights reserved.