EFFICACY OF COMPETITIVE VS NONCOMPETITIVE BLOCKADE OF THE NMDA CHANNEL FOLLOWING TRAUMATIC BRAIN INJURY

N-methyl-D-aspartate (NMDA) receptor antagonists have been demonstrate d widely to be neuroprotective in cerebral ischemia, hypoxia, and trau matic brain injury. However, although noncompetitive NMDA antagonists have typically proven efficacious under all of these conditions, compe titive antagonists have not been shown to be beneficial following mode rate traumatic brain injury. The present study has used phosphorus mag netic resonance spectroscopy ([P-31]MRS) to examine the effects of the competitive antagonist cis-4-(phosphonomethyl) piperidine-2-carboxyli c acid (CGS-19755) and the noncompetitive antagonist dextromethorphan on biochemical outcome following fluid percussion-induced traumatic br ain injury in rats. Five minutes prior to induction of moderate (2.8 /- 0.2 atm) fluid percussion brain injury, animals received either CGS -19755 (10 mg/kg iv), dextromethorphan (10 mg/kg iv), or equal volume saline vehicle. [P-31]MRS spectra were then acquired for 4 h post-trau ma and intracellular pH, free magnesium concentration, cytosolic phosp horylation potential, and oxidative capacity determined. Both CGS-1975 5-treated animals and saline treated controls demonstrated significant and sustained declines in intracellular free magnesium concentration and bioenergetic status following trauma. In contrast, administration of dextromethorphan significantly attenuated free magnesium decline an d improved bioenergetic state during the post-traumatic monitoring per iod. These results suggest that the neuroprotective actions of NMDA an tagonists following traumatic brain injury are associated with attenua tion of free magnesium decline and that such actions seem to be prefer entially medicated by noncompetitive blockers.