Hyperhomocysteinemia-Induced Oxidative Stress Exacerbates Cortical Traumatic Brain Injury Outcomes in Rats.
Animals
Anxiety
/ blood
Behavior, Animal
/ drug effects
Blood Coagulation
/ drug effects
Blood-Brain Barrier
/ drug effects
Brain Injuries, Traumatic
/ blood
Cerebral Cortex
/ pathology
Homocysteine
/ blood
Hyperhomocysteinemia
/ blood
Inflammation
/ blood
Intercellular Adhesion Molecule-1
/ metabolism
Male
Methionine
/ administration & dosage
Occludin
/ metabolism
Oxidative Stress
/ drug effects
Rats, Sprague-Dawley
Tyrosine
/ analogs & derivatives
Zonula Occludens-1 Protein
/ metabolism
Heterogeneity
Hyperhomocysteinemia
Pathophysiology
Stress
Traumatic-brain injury
Journal
Cellular and molecular neurobiology
ISSN: 1573-6830
Titre abrégé: Cell Mol Neurobiol
Pays: United States
ID NLM: 8200709
Informations de publication
Date de publication:
Apr 2021
Apr 2021
Historique:
received:
19
02
2020
accepted:
05
05
2020
pubmed:
15
5
2020
medline:
1
10
2021
entrez:
15
5
2020
Statut:
ppublish
Résumé
Traumatic brain injury (TBI) is a leading cause of morbidity and mortality among military service members and civilians in the United States. Despite significant advances in the understanding of TBI pathophysiology, several clinical reports indicate that multiple genetic and epigenetic factors can influence outcome. Homocysteine (HCY) is a non-proteinogenic amino acid, the catabolism of which can be dysregulated by stress, lifestyle, aging, or genetic abnormalities leading to hyperhomocysteinemia (HHCY). HHCY is a neurotoxic condition and a risk factor for multiple neurological and cardiovascular disorders that occurs when HCY levels is clinically > 15 µM. Although the deleterious impact of HHCY has been studied in human and animal models of neurological disorders such as stroke, Alzheimer's disease and Parkinson's disease, it has not been addressed in TBI models. This study tested the hypothesis that HHCY has detrimental effects on TBI pathophysiology. Moderate HHCY was induced in adult male Sprague Dawley rats via daily administration of methionine followed by impact-induced traumatic brain injury. In this model, HHCY increased oxidative stress, upregulated expression of proteins that promote blood coagulation, exacerbated TBI-associated blood-brain barrier dysfunction and promoted the infiltration of inflammatory cells into the cortex. We also observed an increase of brain injury-induced lesion size and aggravated anxiety-like behavior. These findings show that moderate HHCY exacerbates TBI outcomes and suggest that HCY catabolic dysregulation may be a significant biological variable that could contribute to TBI pathophysiology heterogeneity.
Identifiants
pubmed: 32405706
doi: 10.1007/s10571-020-00866-7
pii: 10.1007/s10571-020-00866-7
doi:
Substances chimiques
Occludin
0
Zonula Occludens-1 Protein
0
Homocysteine
0LVT1QZ0BA
Intercellular Adhesion Molecule-1
126547-89-5
3-nitrotyrosine
3604-79-3
Tyrosine
42HK56048U
Methionine
AE28F7PNPL
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
487-503Subventions
Organisme : Air Force Office of Scientific Research
ID : FA8650-17-2-6H10
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