Hyperhomocysteinemia-Induced Oxidative Stress Exacerbates Cortical Traumatic Brain Injury Outcomes in Rats

Springer Science and Business Media LLC - Tập 41 - Trang 487-503 - 2020
Flaubert Tchantchou1, Molly Goodfellow1, Fengying Li1, Lyric Ramsue1, Catriona Miller2, Adam Puche3, Gary Fiskum1
1Department of Anesthesiology and the Center for Shock, Trauma and Anesthesiology Research (STAR), University of Maryland School of Medicine, Baltimore, USA
2Aeromedical Research, U.S Air Force School of Aerospace Medicine, Dayton, USA
3Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, USA

Tóm tắt

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.

Tài liệu tham khảo

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