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.