Cited by 202Neuroinflammation and Neurodegeneration MechanismsRedox biology and oxidative stressInflammasome and immune disorders

NADPH oxidase- and mitochondria-derived reactive oxygen species in proinflammatory microglial activation: A bipartisan affair?

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Bordt, Evan A., Polster, Brian M.·2014·Free Radical Biology and Medicine

Abstract

Microglia are the resident immune cells of the brain and play major roles in central nervous system development, maintenance, and disease. Brain insults cause microglia to proliferate, migrate, and transform into one or more activated states. Classical M1 activation triggers the production of proinflammatory factors such as tumor necrosis factor-α, interleukin-1β (IL-1β), nitric oxide, and reactive oxygen species (ROS), which, in excess, can exacerbate brain injury. The mechanisms underlying microglial activation are not fully understood, yet reactive oxygen species are increasingly implicated as mediators of microglial activation. In this review, we highlight studies linking reactive oxygen species, in particular hydrogen peroxide derived from NADPH oxidase-generated superoxide, to the classical activation of microglia. In addition, we critically evaluate controversial evidence suggesting a specific role for mitochondrial reactive oxygen species in the activation of the NLRP3 inflammasome, a multiprotein complex that mediates the production of IL-1β and IL-18. Finally, the limitations of common techniques used to implicate mitochondrial ROS in microglial and inflammasome activation, such as the use of the mitochondrially targeted ROS indicator MitoSOX and the mitochondrially targeted antioxidant MitoTEMPO, are also discussed.

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Crossref · 10.1016/j.freeradbiomed.2014.07.033

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  1. [50]Kumar A Loane DJ Neuroinflammation after traumatic brain injury: opportunities for therapeutic intervention Brain Behav Immun 26 1191 201 2012 22728326

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Authors
Bordt, E. A., & Polster, B. M.
Affiliations
University of Maryland, Baltimore (US)
Corresponding author
Polster, Brian M.
Venue
Free Radical Biology and Medicine
Publisher
Elsevier BV
Published
2014-11
Volume
76
Pages
34-46
ISSN
0891-5849 (ISSN-L)
OpenAlex
W1971167579
Cited by
202
References
163
Citations by year
2026: 15 · 2025: 15 · 2024: 17 · 2023: 14 · 2022: 19 · 2021: 24 · 2020: 16 · 2019: 18 · 2018: 20 · 2017: 16 · 2016: 15 · 2015: 12 · 2014: 1
FWCI
1.19
Type
journal article
Language
en
Open access
Locations
  • Free Radical Biology and Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institutes of Health (R01 NS085165)
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
Keywords
microglial activation, reactive oxygen species, NADPH oxidase, mitochondrial reactive oxygen species, hydrogen peroxide, superoxide, M1 macrophage polarization, NLRP3 inflammasome, IL-1β, IL-18, MitoSOX, MitoTEMPO, neuroinflammation, brain injury
MeSH terms
Animals, Humans, Mitochondria, Reactive Oxygen Species, Microglia, Inflammation Mediators, NADPH Oxidases

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