Open AccessSeverity of experimental traumatic brain injury modulates changes in concentrations of cerebral free amino acids
Author(s) -
Amorini Angela Maria,
Lazzarino Giacomo,
Di Pietro Valentina,
Signoretti Stefano,
Lazzarino Giuseppe,
Belli Antonio,
Tavazzi Barbara
Publication year - 2017
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12998
Subject(s) - amino acid , glutamine , valine , traumatic brain injury , leucine , methionine , taurine , arginine , glycine , excitotoxicity , alanine , phenylalanine , creatine , glutamate receptor , citrulline , isoleucine , biochemistry , chemistry , medicine , receptor , psychiatry
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.