THE VULNERABILITY OF SPINAL-CORD NEURONS TO EXCITOTOXIC INJURY - COMPARISON WITH CORTICAL-NEURONS

The neurotoxicity of the glutamate receptor agonists N-methyl-D-aspart ate (NMDA), lpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (A MPA), and kainate was quantitatively assessed in murine spinal cord an d cortical cultures prepared under identical conditions. Compared with cortical neurons, spinal neurons were less vulnerable to NMDA (EC(50) for 24 h exposure about 30 mu M versus 10 mu M in cortical cultures) and more vulnerable to AMPA (EC(50) 5 mu M versus 12 mu M) and kainate (EC(50) 20 mu M versus 50 mu M). Neurons subject to kainate-activated cobalt uptake, a marker of calcium-permeable AMPA/kainate channels, w ere resistant to NMDA in both systems; these cells were significantly more prevalent in spinal cord cultures. Both the AMPA/kainate antagoni st GYKI-52466 and the NMDA antagonist MK-801 attenuated spinal cord ne uronal loss due to glucose deprivation; however, GYKI-52466 was more e ffective. These results support the hypothesis that AMPA/kainate recep tor activation may play a significant role in excitotoxic injury to sp inal cord neurons.