TRAUMATIC BRAIN INJURY-INDUCED EXCITOTOXICITY ASSESSED IN A CONTROLLED CORTICAL IMPACT MODEL

Using a controlled cortical impact model of traumatic brain injury (TB I) coupled with tissue microdialysis, interstitial concentrations of a spartate and glutamate (together with serine and glutamine) were asses sed in rat frontal cortex. Histological analysis indicated that the se verity of injury following severe TBI (depth of deformation = 3.5 mm) was approximately twice that occurring following moderate TBI (depth o f deformation = 1.5 mm). Both groups demonstrated significant postinju ry maximal increases in excitatory amino acid (EAA) concentration, whi ch were proportional to the severity of injury. The mean +/- SEM fold increase in dialysate concentrations of aspartate was 38 +/- 13 (n = 5 ) for moderate TBI and 74 +/- 12 (n = 5) for severe TBI. Fold increase s in glutamate concentrations were 81 +/- 26 and 144 +/- 23 for modera te and severe TBI, respectively. Although these increases normalized w ithin 20-30 min following moderate TBI, concentrations of aspartate an d glutamate took >60 min to normalize after severe TBI. Changes in lev els of nontransmitter amino acids were much smaller. Fold increases fo r serine concentrations were 4.6 +/- 0.6 and 7.6 +/- 1.7 in moderate a nd severe TBI, respectively; glutamine concentrations had similar smal l fold increases (2.6 +/- 0.2 and 4.1 +/- 0.6, respectively). Calculat ion of interstitial concentrations following severe TBI indicated that aspartate and glutamate maximally increased to 123 +/- 20 and 414 +/- 66 muM, respectively. To determine the extent to which such tissue co ncentrations of EAAs could contribute to the injury seen in TBI, the E AA receptor agonists N-methyl-D-aspartate and pha-amino-3-hydroxy-5-me thyl-4-isoxazole-propionic acid were slowly injected into rat cortex. Remarkably similar histological injuries were produced by this procedu re, supporting the notion that TBI is an excitotoxic injury.