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 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.
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Division of Neurosurgery, Toronto Western Hospital, Canada.
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D000818:Animals; D002531:Cerebellum / Q000503:physiopathology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D005071:Evoked Potentials / Q000187:drug effects; D019054:Evoked Potentials, Motor / Q000187:drug effects; D005073:Evoked Potentials, Somatosensory / Q000187:drug effects; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D008297:Male; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors*; D018092:Kainic Acid Receptors / Q000037:antagonists & inhibitors*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D012039:Regional Blood Flow / Q000187:drug effects; D013116:Spinal Cord / Q000098:blood supply / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000188:drug therapy*
D016291:Dizocilpine Maleate; D018691:Excitatory Amino Acid Antagonists; D011810:Quinoxalines; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline