PMID- 32405706
OWN - NLM
STAT- MEDLINE
DCOM- 20210930
LR  - 20240226
IS  - 1573-6830 (Electronic)
IS  - 0272-4340 (Linking)
VI  - 41
IP  - 3
DP  - 2021 Apr
TI  - Hyperhomocysteinemia-Induced Oxidative Stress Exacerbates Cortical Traumatic 
      Brain Injury Outcomes in Rats.
PG  - 487-503
LID - 10.1007/s10571-020-00866-7 [doi]
AB  - 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 microM. 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.
FAU - Tchantchou, Flaubert
AU  - Tchantchou F
AUID- ORCID: 0000-0002-9513-5535
AD  - Department of Anesthesiology and the Center for Shock, Trauma and Anesthesiology 
      Research (STAR), University of Maryland School of Medicine, 685 W. Baltimore 
      Street, Baltimore, MD, 21201, USA. ftchantchou@som.umaryland.edu.
FAU - Goodfellow, Molly
AU  - Goodfellow M
AD  - Department of Anesthesiology and the Center for Shock, Trauma and Anesthesiology 
      Research (STAR), University of Maryland School of Medicine, 685 W. Baltimore 
      Street, Baltimore, MD, 21201, USA.
FAU - Li, Fengying
AU  - Li F
AD  - Department of Anesthesiology and the Center for Shock, Trauma and Anesthesiology 
      Research (STAR), University of Maryland School of Medicine, 685 W. Baltimore 
      Street, Baltimore, MD, 21201, USA.
FAU - Ramsue, Lyric
AU  - Ramsue L
AD  - Department of Anesthesiology and the Center for Shock, Trauma and Anesthesiology 
      Research (STAR), University of Maryland School of Medicine, 685 W. Baltimore 
      Street, Baltimore, MD, 21201, USA.
FAU - Miller, Catriona
AU  - Miller C
AD  - Aeromedical Research, U.S Air Force School of Aerospace Medicine, Dayton, OH, 
      USA.
FAU - Puche, Adam
AU  - Puche A
AD  - Department of Anatomy and Neurobiology, University of Maryland School of 
      Medicine, Baltimore, MD, USA.
FAU - Fiskum, Gary
AU  - Fiskum G
AD  - Department of Anesthesiology and the Center for Shock, Trauma and Anesthesiology 
      Research (STAR), University of Maryland School of Medicine, 685 W. Baltimore 
      Street, Baltimore, MD, 21201, USA.
LA  - eng
GR  - FA8650-17-2-6H10/Air Force Office of Scientific Research/
PT  - Journal Article
DEP - 20200513
PL  - United States
TA  - Cell Mol Neurobiol
JT  - Cellular and molecular neurobiology
JID - 8200709
RN  - 0 (Occludin)
RN  - 0 (Zonula Occludens-1 Protein)
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
RN  - 3604-79-3 (3-nitrotyrosine)
RN  - 42HK56048U (Tyrosine)
RN  - AE28F7PNPL (Methionine)
SB  - IM
MH  - Animals
MH  - Anxiety/blood/complications
MH  - Behavior, Animal/drug effects
MH  - Blood Coagulation/drug effects
MH  - Blood-Brain Barrier/drug effects/pathology/physiopathology
MH  - Brain Injuries, Traumatic/blood/*etiology/*pathology
MH  - Cerebral Cortex/*pathology
MH  - Homocysteine/blood/toxicity
MH  - Hyperhomocysteinemia/blood/*complications
MH  - Inflammation/blood/pathology
MH  - Intercellular Adhesion Molecule-1/metabolism
MH  - Male
MH  - Methionine/administration & dosage
MH  - Occludin/metabolism
MH  - *Oxidative Stress/drug effects
MH  - Rats, Sprague-Dawley
MH  - Tyrosine/analogs & derivatives/metabolism
MH  - Zonula Occludens-1 Protein/metabolism
MH  - Rats
OTO - NOTNLM
OT  - Heterogeneity
OT  - Hyperhomocysteinemia
OT  - Pathophysiology
OT  - Stress
OT  - Traumatic-brain injury
EDAT- 2020/05/15 06:00
MHDA- 2021/10/01 06:00
CRDT- 2020/05/15 06:00
PHST- 2020/02/19 00:00 [received]
PHST- 2020/05/05 00:00 [accepted]
PHST- 2020/05/15 06:00 [pubmed]
PHST- 2021/10/01 06:00 [medline]
PHST- 2020/05/15 06:00 [entrez]
AID - 10.1007/s10571-020-00866-7 [pii]
AID - 10.1007/s10571-020-00866-7 [doi]
PST - ppublish
SO  - Cell Mol Neurobiol. 2021 Apr;41(3):487-503. doi: 10.1007/s10571-020-00866-7. Epub 
      2020 May 13.