PMID- 28774719 OWN - NLM STAT- MEDLINE DCOM- 20190215 LR - 20190215 IS - 1872-9754 (Electronic) IS - 0197-0186 (Linking) VI - 112 DP - 2018 Jan TI - Defective methionine metabolism in the brain after repeated blast exposures might contribute to increased oxidative stress. PG - 234-238 LID - S0197-0186(17)30367-4 [pii] LID - 10.1016/j.neuint.2017.07.014 [doi] AB - Blast-induced traumatic brain injury (bTBI) is one of the major disabilities in Service Members returning from recent military operations. The neurobiological underpinnings of bTBI, which are associated with acute and chronic neuropathological and neurobehavioral deficits, are uncertain. Increased oxidative stress in the brain is reported to play a significant role promoting neuronal damage associated with both brain injury and neurodegenerative disorders. In this study, brains of rats exposed to repeated blasts in a shock tube underwent untargeted profiling of primary metabolism by automatic linear exchange/cold injection GC-TOF mass spectrometry and revealed acute and sub-acute disruptions in the metabolism of the essential amino acid methionine and associated antioxidants. Methionine sulfoxide, the oxidized metabolite of methionine, showed a sustained increase in the brain after blast exposure which was associated with a significant decrease in cysteine, the amino acid derived from methionine. Glutathione, the antioxidant synthesized from cysteine, also concomitantly decreased as did the antioxidant ascorbic acid. Reductions in ascorbic acid were accompanied by increased levels of its oxidized metabolite, dehydroascorbic acid and other metabolites such as threonic acid, isothreonic acid, glycolic acid and oxalic acid. Fluorometric analysis of the brains showed acute and sub-acute increase in total reactive oxygen species. In view of the fundamental importance of glutathione in the brain as an antioxidant, including its role in the reduction of dehydroascorbic acid to ascorbic acid, the disruptions in methionine metabolism elicited by blast exposure might prominently contribute to neuronal injury by promoting increased and sustained oxidative stress. CI - Copyright (c) 2017 Elsevier Ltd. All rights reserved. FAU - Arun, Peethambaran AU - Arun P AD - Blast-Induced Neurotrauma Branch, Center for Military Psychiatry and Neuroscience, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA. Electronic address: peethambaran.arun.ctr@mail.mil. FAU - Rittase, William B AU - Rittase WB AD - Blast-Induced Neurotrauma Branch, Center for Military Psychiatry and Neuroscience, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA. FAU - Wilder, Donna M AU - Wilder DM AD - Blast-Induced Neurotrauma Branch, Center for Military Psychiatry and Neuroscience, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA. FAU - Wang, Ying AU - Wang Y AD - Blast-Induced Neurotrauma Branch, Center for Military Psychiatry and Neuroscience, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA. FAU - Gist, Irene D AU - Gist ID AD - Blast-Induced Neurotrauma Branch, Center for Military Psychiatry and Neuroscience, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA. FAU - Long, Joseph B AU - Long JB AD - Blast-Induced Neurotrauma Branch, Center for Military Psychiatry and Neuroscience, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA. Electronic address: joseph.b.long.civ@mail.mil. LA - eng PT - Journal Article PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20170731 PL - England TA - Neurochem Int JT - Neurochemistry international JID - 8006959 RN - 0 (Reactive Oxygen Species) RN - AE28F7PNPL (Methionine) SB - IM MH - Animals MH - Blast Injuries/*metabolism/pathology MH - Brain/*metabolism/pathology MH - Brain Injuries/*metabolism/pathology MH - Male MH - Methionine/*metabolism MH - Oxidative Stress/*physiology MH - Rats MH - Rats, Sprague-Dawley MH - Reactive Oxygen Species/metabolism OTO - NOTNLM OT - Antioxidants OT - Ascorbic acid OT - Blast exposure OT - Cysteine OT - Glutathione OT - Methionine OT - Oxidative stress OT - Traumatic brain injury EDAT- 2017/08/05 06:00 MHDA- 2019/02/16 06:00 CRDT- 2017/08/05 06:00 PHST- 2017/06/22 00:00 [received] PHST- 2017/07/29 00:00 [accepted] PHST- 2017/08/05 06:00 [pubmed] PHST- 2019/02/16 06:00 [medline] PHST- 2017/08/05 06:00 [entrez] AID - S0197-0186(17)30367-4 [pii] AID - 10.1016/j.neuint.2017.07.014 [doi] PST - ppublish SO - Neurochem Int. 2018 Jan;112:234-238. doi: 10.1016/j.neuint.2017.07.014. Epub 2017 Jul 31.