Deletion of NADPH oxidase 4 reduces severity of traumatic brain injury

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Traumatic brain injury (TBI) contributes to over 30% of injury-related deaths and is a major cause of disability without effective clinical therapies. Oxidative stress contributes to neurodegeneration, neuroinflammation, and neuronal death to amplify the primary injury after TBI. NADPH oxidase (NOX) is a major source of reactive oxygen species following brain injury. Our current study addresses the functional role of the NOX4 isoform in the damaged cortex following TBI. Adult male C57BL/6 J and NOX4 -/- mice received a controlled cortical impact and lesion size, NOX4 expression, oxidative stress, neurodegeneration, and cell death were assessed in the injured cerebral cortex. The results revealed that NOX4 mRNA and protein expression were significantly upregulated at 1–7 days post-TBI in the injured cerebral cortex. Expression of the oxidative stress markers, 8-OHdG, 4-HNE, and nitrotyrosine was upregulated at 2 and 4 days post-TBI in the WT injured cerebral cortex, and nitrotyrosine primarily colocalized with neurons. In the NOX4 -/- mice, expression of these oxidative stress markers, 8-OHdG, 4-HNE, and nitrotyrosine were significantly attenuated at both timepoints. In addition, examination of NOX4 -/- mice revealed a reduced number of apoptotic (TUNEL + ) and degenerating (FJB + ) cells in the perilesional cortex after TBI, as well as a smaller lesion size compared with the WT group. The results of this study implicate a functional role for NOX4 in TBI induced oxidative damage and neurodegeneration and raise the possibility that targeting NOX4 may have therapeutic efficacy in TBI.

Original languageEnglish (US)
Pages (from-to)66-75
Number of pages10
JournalFree Radical Biology and Medicine
Volume117
DOIs
StatePublished - Mar 1 2018

Keywords

  • NADPH oxidase
  • NOX4
  • Oxidative stress
  • TBI
  • Traumatic brain injury

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

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