Experimental neurology
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Experimental neurology · Jun 1997
Delayed antagonism of AMPA/kainate receptors reduces long-term functional deficits resulting from spinal cord trauma.
Excitatory amino acid (EAA) receptors play a significant role in delayed neuronal death after ischemic and traumatic injury to the CNS. Focal microinjection experiments have demonstrated that 2,3-dihydro-6-nitro-7-sulfamoyl-benzo(f)quinoxaline (NBQX), a highly selective and potent antagonist of non-N-methyl-D-aspartate ionotropic EAA receptors, i.e., those preferring alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) or kainate, can reduce histopathology and functional deficits when administered at 15 min after traumatic spinal cord injury (SCI). Similarly, intravenous infusion of NBQX, beginning at 15 min postinjury (p.i.), results in a significant amelioration of the functional deficits produced by experimental SCI. ⋯ These results support a therapeutic potential for NBQX, and presumably other AMPA antagonists, in SCI by demonstrating effectiveness in a clinically relevant time frame. They indicate the importance of assessing chronic functional deficits in evaluating the therapeutic potential of a treatment paradigm. Further, they suggest the intriguing hypothesis that mechanisms underlying early functional recovery after SCI are, at least in part, distinct those from those involved in reducing chronic functional deficits.