title: Severity of experimental traumatic brain injury modulates changes in concentrations of cerebral free amino acids.
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.
authors.affiliation: Institute of Biochemistry and Clinical Biochemistry, Catholic University of Rome, Rome, Italy.
authors.forename: Angela Maria
authors.initials: AM
authors.lastname: Amorini
authors.affiliation: Institute of Biochemistry and Clinical Biochemistry, Catholic University of Rome, Rome, Italy.
authors.forename: Giacomo
authors.initials: G
authors.lastname: Lazzarino
authors.affiliation: Neuroscience and Ophthalmology group, School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
authors.forename: Valentina
authors.initials: V
authors.lastname: Di Pietro
authors.affiliation: Division of Neurosurgery, Department of Neurosciences Head and Neck Surgery, S. Camillo Hospital, Rome, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Signoretti
authors.affiliation: Division of Medical Biochemistry, Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy.
authors.forename: Giuseppe
authors.identifier: 0000-0002-5917-7279
authors.initials: G
authors.lastname: Lazzarino
authors.affiliation: Neuroscience and Ophthalmology group, School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.|National Institute for Health Research Surgical Reconstruction and Microbiology Research Centre, Queen Elizabeth Hospital, Birmingham, UK.
authors.forename: Antonio
authors.initials: A
authors.lastname: Belli
authors.affiliation: Institute of Biochemistry and Clinical Biochemistry, Catholic University of Rome, Rome, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Tavazzi
mesh_terms: D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D000070642:Brain Injuries, Traumatic / Q000378:metabolism / Q000473:pathology*; D008297:Male; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000596:Amino Acids
keywords: N-acetylaspartate; cerebral free amino acids; excitotoxicity; high performance liquid chromatography; methyl-cycle; mild traumatic brain injury; severe traumatic brain injury