Severity of experimental traumatic brain injury modulates changes in concentrations of cerebral free amino acids |
| |
| Authors: | Valentina Di Pietro Stefano Signoretti Giuseppe Lazzarino Antonio Belli Barbara Tavazzi |
| |
| Affiliation: | 1. Neuroscience and Ophthalmology group, School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK;2. Division of Neurosurgery, Department of Neurosciences Head and Neck Surgery, S. Camillo Hospital, Rome, Italy;3. Division of Medical Biochemistry, Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy;4. National Institute for Health Research Surgical Reconstruction and Microbiology Research Centre, Queen Elizabeth Hospital, Birmingham, UK;5. Institute of Biochemistry and Clinical Biochemistry, Catholic University of Rome, Rome, Italy |
| |
| 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. |
| |
| Keywords: | cerebral free amino acids excitotoxicity high performance liquid chromatography methyl‐cycle N‐acetylaspartate mild traumatic brain injury severe traumatic brain injury |
|
|
