Hypothesis of the Postconcussive Vulnerable Brain: Experimental Evidence of Its Metabolic Occurrence

Abstract

We evaluated the effects of two consecutive concussive injuries on brain energy metabolism and N-acetylaspartate (NAA) to investigate how the temporal interval between traumatic events influences overall injury severity. Rats were injured to induce diffuse traumatic brain injury (TBI) (mild, 450 g/1 m; severe, 450 g/2 m). In two groups, two mild TBIs were delivered in 3- or 5-day intervals. Three additional animal groups were used: single mild TBI, single severe TBI, and sham. All animals were killed 48 hours postinjury. Adenosine 5'-triphosphate (ATP), adenosine diphosphate, and NAA concentrations were analyzed with high-performance liquid chromatography on deproteinized whole brain extracts. In control animals, the NAA concentration was 9.17 +/- 0.38 micromol/g wet weight, the ATP concentration was 2.25 +/- 0.21 micromol/g wet weight, and the ATP-to-adenosine diphosphate ratio was 9.38 +/- 1.23. These concentrations decreased to 6.68 +/- 1.12 micromol/g wet weight, 1.68 +/- 0.24 micromol/g wet weight, and 6.10 +/- 1.21 micromol/g wet weight, respectively, in rats that received two mild TBIs at a 5-day interval (P < 0.01; not different from results in rats with single mild TBI). When a second TBI was delivered after 3 days, the NAA concentration was 3.86 +/- 0.53 micromol/g wet weight, the ATP concentration was 1.11 +/- 0.18 micromol/g wet weight, and the ATP-to-adenosine diphosphate ratio was 2.64 +/- 0.43 (P < 0.001 versus both controls and 3-day interval; not different from rats receiving a single severe TBI). The biochemical modification severity in double TBI is dependent on the interval between traumatic events, which demonstrates the metabolic state of the vulnerable brain after mild TBI. These data support the hypothesis of the application of proton magnetic resonance spectroscopy to measure NAA as a possible tool to monitor the full recovery of brain metabolic functions in the clinical setting, particularly in sports medicine.