Traumatic brain injury induces region-specific glutamate metabolism changes as measured by multiple mass spectrometry methods.
Metabolomics
Molecular physiology
Neuroscience
Journal
iScience
ISSN: 2589-0042
Titre abrégé: iScience
Pays: United States
ID NLM: 101724038
Informations de publication
Date de publication:
22 Oct 2021
22 Oct 2021
Historique:
received:
05
10
2020
revised:
14
06
2021
accepted:
08
09
2021
entrez:
8
10
2021
pubmed:
9
10
2021
medline:
9
10
2021
Statut:
epublish
Résumé
The release of excess glutamate following traumatic brain injury (TBI) results in glutamate excitotoxicity and metabolic energy failure. Endogenous mechanisms for reducing glutamate concentration in the brain parenchyma following TBI are poorly understood. Using multiple mass spectrometry approaches, we examined TBI-induced changes to glutamate metabolism. We present evidence that glutamate concentration can be reduced by glutamate oxidation via a "truncated" tricarboxylic acid cycle coupled to the urea cycle. This process reduces glutamate levels, generates carbon for energy metabolism, leads to citrulline accumulation, and produces nitric oxide. Several key metabolites are identified by metabolomics in support of this mechanism and the locations of these metabolites in the injured hemisphere are demonstrated by MALDI-MS imaging. The results of this study establish the advantages of multiple mass spectrometry approaches and provide insights into glutamate metabolism following TBI that could lead to improved treatment approaches.
Identifiants
pubmed: 34622161
doi: 10.1016/j.isci.2021.103108
pii: S2589-0042(21)01076-2
pmc: PMC8479783
doi:
Types de publication
Journal Article
Langues
eng
Pagination
103108Informations de copyright
© 2021 The Authors.
Déclaration de conflit d'intérêts
The authors declare no competing interests.
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