NADPH oxidases in traumatic brain injury – Promising therapeutic targets?

Merry W. Ma, Jing Wang, Krishnan M. Dhandapani, Ruimin Wang, Darrell W. Brann

Research output: Contribution to journalShort surveypeer-review

80 Scopus citations

Abstract

Traumatic brain injury (TBI) is a major cause of death and disability worldwide. Despite intense investigation, no neuroprotective agents for TBI have yet translated to the clinic. Recent efforts have focused on identifying potential therapeutic targets that underlie the secondary TBI pathology that evolves minutes to years following the initial injury. Oxidative stress is a key player in this complex cascade of secondary injury mechanisms and prominently contributes to neurodegeneration and neuroinflammation. NADPH oxidase (NOX) is a family of enzymes whose unique function is to produce reactive oxygen species (ROS). Human post-mortem and animal studies have identified elevated NOX2 and NOX4 levels in the injured brain, suggesting that these two NOXs are involved in the pathogenesis of TBI. In support of this, NOX2 and NOX4 deletion studies have collectively revealed that targeting NOX enzymes can reduce oxidative stress, attenuate neuroinflammation, promote neuronal survival, and improve functional outcomes following TBI. In addition, NOX inhibitor studies have confirmed these findings and demonstrated an extended critical window of efficacious TBI treatment. Finally, the translational potential, caveats, and future directions of the field are highlighted and discussed throughout the review.

Original languageEnglish (US)
Pages (from-to)285-293
Number of pages9
JournalRedox Biology
Volume16
DOIs
StatePublished - Jun 2018

Keywords

  • Apocynin
  • CCI
  • CHI
  • Controlled cortical impact
  • FPI
  • Microglia
  • NADPH oxidase
  • NOX
  • NOX1
  • NOX2
  • NOX4
  • Oxidative stress
  • ROS
  • TBI
  • Traumatic brain injury
  • gp91ds-tat

ASJC Scopus subject areas

  • Organic Chemistry

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