N-acetylaspartate reduction as a measure of injury severity and mitochondrial dysfunction following diffuse traumatic brain injury

N-Acetylaspartate (NAA) is considered a neuron-specific metabolite and its reduction a marker of neuronal loss. The objective of this study was to eva luate the time course of NAA changes in varying grades of traumatic brain i njury (TBI), in concert with the disturbance of energy metabolites (ATP). S ince NAA is synthesized by the mitochondria, it was hypothesized that chang es in NAA would follow ATP. The impact acceleration model was used to produ ce three grades of TBI. Sprague-Dawley rats were divided into the following four-groups: sham control (n = 12); moderate TBI (n = 36); severe TBI (n = 36); and severe TBI coupled with hypoxia-hypotension (n = 16). Animals wer e sacrificed at different time points ranging from I min to 120 h postinjur y, and the brain was processed for high-performance liquid chromatography ( HPLC) analysis of NAA and ATP. After moderate TBI, NAA reduced gradually by 35% at 6 h and 46% at 15 h, accompanied by a 57% and 45% reduction in ATP. A spontaneous recovery of NAA to 86% of baseline at 120 h was paralleled b y a restoration in ATP. In severe TBI, NAA fell suddenly and did not recove r, showing critical reduction (60%) at 48 h. ATP was reduced by 70% and als o did not recover. Maximum NAA and ATP decrease occurred with secondary ins ult (80% and 90%, respectively, at 48 h). These data show that, at 48 h pos t diffuse TBI, reduction of NAA is graded according to the severity of insu lt. NAA recovers if the degree of injury is moderate and not accompanied by secondary insult. The highly similar time course and correlation between N AA and ATP supports the notion that NAA reduction is related to energetic i mpairment.