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Oxidative stress contributes to cerebral metabolomic profile changes in animal model of blast-induced traumatic brain injury

Authors
  • Rana, Poonam1
  • Rama Rao, Kakulavarapu V.2
  • Ravula, Arunreddy2
  • Trivedi, Richa1
  • D’Souza, Maria1
  • Singh, Ajay K.1
  • Gupta, Raj K.3
  • Chandra, Namas3, 2
  • 1 Institute of Nuclear Medicine and Allied Sciences, Delhi, India , Delhi (India)
  • 2 New Jersey Institute of Technology, Newark, NJ, 07102-1982, USA , Newark (United States)
  • 3 US Army MRMC, 504 Scott Street, Fort Detrick, MD, USA , Fort Detrick (United States)
Type
Published Article
Journal
Metabolomics
Publisher
Springer US
Publication Date
Mar 12, 2020
Volume
16
Issue
3
Identifiers
DOI: 10.1007/s11306-020-1649-4
Source
Springer Nature
Keywords
License
Yellow

Abstract

IntroductionBlast-induced neurotrauma (BINT) has been recognized as the common mode of traumatic brain injury amongst military and civilian personnel due to an increased insurgent activity domestically and abroad. Previous studies from this laboratory have identified three major pathological events following BINT which include blood brain barrier disruption the earliest event, followed by oxidative stress and neuroinflammation as secondary events occurring a few hours following blast.ObjectivesOur recent studies have also identified an increase in oxidative stress mediated by the activation of superoxide producing enzyme NADPH oxidase (NOX) in different brain regions at varying levels with neurons displaying higher oxidative stress (NOX activation) compared to any other neural cell. Since neurons have higher energy demands in brain and are more prone to oxidative damage, this study evaluated the effect of oxidative stress on blast-blast induced changes in metabolomics profiles in different brain regions.MethodsAnimals were exposed to mild/moderate blast injury (180 kPa) and examined the metabolites of energy metabolism, amino acid metabolism as well as the profiles of plasma membrane metabolites in different brain regions at different time points (24 h, 3 day and 7 day) after blast using 1H NMR spectroscopy. Effect of apocynin, an inhibitor of superoxide producing enzyme NADPH oxidase on cerebral metabalomics profiles was also examined.ResultsSeveral metabolomic profile changes were observed in frontal cortex and hippocampus with concomitant decrease in energy metabolism. In addition, glutamate/glutamine and other amino acid metabolism as well as metabolites involved in plasma membrane integrity were also altered. Hippocampus appears metabolically more vulnerable than the frontal cortex. A post-treatment of animals with apocynin, an inhibitor of NOX activation significantly prevented the changes in metabolite profiles.ConclusionTogether these studies indicate that blast injury reduces both cerebral energy and neurotransmitter amino acid metabolism and that oxidative stress contributes to these processes. Thus, strategies aimed at reducing oxidative stress can have a therapeutic benefit in mitigating metabolic changes following BINT.

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