Action of locally administered NMDA and AMPA/kainate receptor antagonists in spinal cord injury

NMDA or AMPA/kainate receptor antagonists have been shown to provide neurop rotection following in vitro spinal cord injury, but the mechanisms by whic h these agents improve behavioral recovery and protect axonal function rema ins unclear. We hypothesized that treatment of spinal cord injury with thes e drugs would attenuate glutamate excitatory transmission by blocking the e ffects of glutamate receptors at the injury site or would improve spinal co rd blood flow To test these hypotheses, we observed the effects of locally administered MK-801 (30 nmol) or NBQX (5 or 15 nmol) into the injured spina l cord on axonal conduction and post-traumatic ischemia of the cord. The ou tcome measures were multimodality evoked potentials and blood flow in an ac ute compression injury model in rats. We found that locally administered MK -801 or NBQX 15 min after spinal cord injury attenuated the amplitude, dela yed the latency of sensory evoked potentials and increased the sensory cond uction time across the injury site, but did not improve blood flow during t he 4-h period of observation. These results demonstrate that the NMDA and n on-NMDA receptor antagonists produced a blockade of glutamate excitatory tr ansmission in the afferent pathways at the injury site. It is suggested tha t the neuroprotection provided by these agents following spinal cord injury is mediated through blockade of glutamate ionotropic receptors in the inju red spinal cord, but is not related to improvement of SCBF.