Abstract
In this study, concentrations of free amino acids (FAA) and amino group containing compounds (AGCC) following graded diffuse traumatic brain injury (mild TBI, mTBI; severe TBI, sTBI) were evaluated. After 6, 12, 24, 48 and 120 hr aspartate (Asp), glutamate (Glu), asparagine (Asn), serine (Ser), glutamine (Gln), histidine (His), glycine (Gly), threonine (Thr), citrulline (Cit), arginine (Arg), alanine (Ala), taurine (Tau), γ‐aminobutyrate (GABA), tyrosine (Tyr), S‐adenosylhomocysteine (SAH), l‐cystathionine (l‐Cystat), valine (Val), methionine (Met), tryptophane (Trp), phenylalanine (Phe), isoleucine (Ile), leucine (Leu), ornithine (Orn), lysine (Lys), plus N‐acetylaspartate (NAA) were determined in whole brain extracts (n = 6 rats at each time for both TBI levels). Sham‐operated animals (n = 6) were used as controls. Results demonstrated that mTBI caused modest, transient changes in NAA, Asp, GABA, Gly, Arg. Following sTBI, animals showed profound, long‐lasting modifications of Glu, Gln, NAA, Asp, GABA, Ser, Gly, Ala, Arg, Citr, Tau, Met, SAH, l‐Cystat, Tyr and Phe. Increase in Glu and Gln, depletion of NAA and Asp increase, suggested a link between NAA hydrolysis and excitotoxicity after sTBI. Additionally, sTBI rats showed net imbalances of the Glu‐Gln/GABA cycle between neurons and astrocytes, and of the methyl‐cycle (demonstrated by decrease in Met, and increase in SAH and l‐Cystat), throughout the post‐injury period. Besides evidencing new potential targets for novel pharmacological treatments, these results suggest that the force acting on the brain tissue at the time of the impact is the main determinant of the reactions ignited and involving amino acid metabolism.
Highlights
IntroductionFree amino acids (FAA) and amino group containing compounds (AGCC), exert fundamental biochemical roles in numerous brain functions
Under physiological conditions, free amino acids (FAA) and amino group containing compounds (AGCC), exert fundamental biochemical roles in numerous brain functions
Glutathione (GSH), the main cerebral low molecular weight antioxidant [8]; Glu is needed for the synthesis of an additional neurotransmitter, namely N-acetylaspartylglutamate (NAAG) [9]; Asp is one of the substrate used for the synthesis of N-acetylaspartate (NAA), the most abundant, neuron specific, N-acetylated amino acid found in the brain [10]; both Asp and Glu participate in the regulation of brain energy metabolism as anaplerotic and cataplerotic compounds of the tricarboxylic acid (TCA) cycle [11]
Summary
Free amino acids (FAA) and amino group containing compounds (AGCC), exert fundamental biochemical roles in numerous brain functions. They can roughly be divided into different categories: (1) those directly involved in neurotransmission, such as glutamate (Glu) and c-aminobutyrric acid (GABA) [1]; (2). Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. Experimental brain ischaemia and reperfusion [14], animal model of amyotrophic lateral sclerosis [15] and experimental seizures [16] have been shown to influence several of the aforementioned substances
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