NMDA or
AMPA/
kainate receptor antagonists have been shown to provide neuroprotection following in vitro
spinal cord injury, but the mechanisms by which these agents improve behavioral recovery and protect axonal function remains unclear. We hypothesized that treatment of
spinal cord injury with these drugs would attenuate
glutamate excitatory transmission by blocking the effects of
glutamate receptors at the injury site or would improve spinal cord 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 spinal cord on axonal conduction and post-traumatic
ischemia of the cord. The outcome measures were multimodality evoked potentials and blood flow in an acute compression injury model in rats. We found that locally administered
MK-801 or
NBQX 15 min after
spinal cord injury attenuated the amplitude, delayed the latency of sensory evoked potentials and increased the sensory conduction time across the injury site, but did not improve blood flow during the 4-h period of observation. These results demonstrate that the
NMDA and non-
NMDA receptor antagonists produced a blockade of
glutamate excitatory transmission in the afferent pathways at the injury site. It is suggested that the neuroprotection provided by these agents following
spinal cord injury is mediated through blockade of
glutamate ionotropic receptors in the injured spinal cord, but is not related to improvement of SCBF.