Pretreatment with NMDA antagonists limits release of excitatory amino acids following traumatic brain injury.
After central nervous system (CNS) trauma, there are marked elevations in the extracellular levels of excitatory amino acids (EAA), which are believed to contribute to delayed tissue damage. Administration of N-methyl-D-aspartate (NMDA) receptor antagonists reduces injury severity after brain or spinal cord trauma, presumably by blocking the postsynaptic NMDA receptor. In the present studies, levels of extracellular amino acids were monitored by microdialysis during, and after, a moderately severe fluid-percussion brain injury to rats. Pretreatment (15 min prior to injury) with the non-competitive NMDA antagonist dextrorphan or the competitive NMDA antagonist CGS 19755 significantly attenuated the post-traumatic increase in extracellular glutamate. Pretreatment with dextrorphan attenuated the post-traumatic increase in extracellular levels of aspartate; although these differences did not reach significance when examined as absolute values, they were significant when analyzed as percent increase over pre-trauma baseline levels. These results are consistent with recent experiments and suggest that NMDA antagonists may limit the release of glutamate and aspartate after trauma through a presynaptic mechanism.
Blood Research Division, Letterman Army Institute of Research, San Francisco, CA 94129.
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D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D001930:Brain Injuries / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D003917:Dextrorphan / Q000494:pharmacology; D003956:Dialysis; D005971:Glutamates / Q000378:metabolism; D018698:Glutamic Acid; D008297:Male; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors*; D010875:Pipecolic Acids / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000187:drug effects
D000596:Amino Acids; D005971:Glutamates; D010875:Pipecolic Acids; D016194:Receptors, N-Methyl-D-Aspartate; D003917:Dextrorphan; D018698:Glutamic Acid; C053672:selfotel; D016202:N-Methylaspartate