Hypobaria-Induced Oxidative Stress Facilitates Homocysteine Transsulfuration and Promotes Glutathione Oxidation in Rats with Mild Traumatic Brain Injury.
Hypobaria
glutathione
homocysteine
oxidative stress
traumatic brain injury
Journal
Journal of central nervous system disease
ISSN: 1179-5735
Titre abrégé: J Cent Nerv Syst Dis
Pays: United States
ID NLM: 101595026
Informations de publication
Date de publication:
2021
2021
Historique:
received:
28
07
2020
accepted:
18
12
2020
entrez:
18
2
2021
pubmed:
19
2
2021
medline:
19
2
2021
Statut:
epublish
Résumé
United States service members injured in combat theatre are often aeromedically evacuated within a few days to regional military hospitals. Animal and epidemiological research indicates that early exposure to flight hypobaria may worsen brain and other injuries. The mechanisms by which secondary exposure to hypobaria worsen trauma outcomes are not well elucidated. This study tested the hypothesis that hypobaria-induced oxidative stress and associated changes in homocysteine levels play a role in traumatic brain injury (TBI) pathological progression caused by hypobaria. Male Sprague Dawley rats were exposed to a 6 h hypobaria 24 h after mild TBI by the controlled cortical impact. Plasma and brain tissues were assessed for homocysteine levels, oxidative stress markers or glutathione metabolism, and behavioral deficits post-injury in the absence and presence of hypobaria exposure. We found that hypobaria after TBI increased oxidative stress markers, altered homocysteine metabolism, and promoted glutathione oxidation. Increased glutathione metabolism was driven by differential upregulation of glutathione metabolizing genes. These changes correlated with increased anxiety-like behavior. These data provide evidence that hypobaria exposure after TBI increases oxidative stress and alters homocysteine elimination likely through enhanced glutathione metabolism. This pathway may represent a compensatory mechanism to attenuate free radical formation. Thus, hypobaria-induced enhancement of glutathione metabolism represents a potential therapeutic target for TBI management.
Sections du résumé
BACKGROUND
BACKGROUND
United States service members injured in combat theatre are often aeromedically evacuated within a few days to regional military hospitals. Animal and epidemiological research indicates that early exposure to flight hypobaria may worsen brain and other injuries. The mechanisms by which secondary exposure to hypobaria worsen trauma outcomes are not well elucidated. This study tested the hypothesis that hypobaria-induced oxidative stress and associated changes in homocysteine levels play a role in traumatic brain injury (TBI) pathological progression caused by hypobaria.
METHODS
METHODS
Male Sprague Dawley rats were exposed to a 6 h hypobaria 24 h after mild TBI by the controlled cortical impact. Plasma and brain tissues were assessed for homocysteine levels, oxidative stress markers or glutathione metabolism, and behavioral deficits post-injury in the absence and presence of hypobaria exposure.
RESULTS
RESULTS
We found that hypobaria after TBI increased oxidative stress markers, altered homocysteine metabolism, and promoted glutathione oxidation. Increased glutathione metabolism was driven by differential upregulation of glutathione metabolizing genes. These changes correlated with increased anxiety-like behavior.
CONCLUSION
CONCLUSIONS
These data provide evidence that hypobaria exposure after TBI increases oxidative stress and alters homocysteine elimination likely through enhanced glutathione metabolism. This pathway may represent a compensatory mechanism to attenuate free radical formation. Thus, hypobaria-induced enhancement of glutathione metabolism represents a potential therapeutic target for TBI management.
Identifiants
pubmed: 33597815
doi: 10.1177/1179573520988193
pii: 10.1177_1179573520988193
pmc: PMC7863175
doi:
Types de publication
Journal Article
Langues
eng
Pagination
1179573520988193Informations de copyright
© The Author(s) 2021.
Déclaration de conflit d'intérêts
Declaration of conflicting interests:The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
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