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Updated: Apr 26, 2026
Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
NADPH oxidase- and mitochondria-derived reactive oxygen species in proinflammatory microglial activation: a
Evan A Bordt1, Brian M Polster1
1Department of Anesthesiology, Center for Shock, Trauma and Anesthesiology Research, and Program in Neuroscience, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
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.
Insights
Reactive oxygen species (ROS), particularly hydrogen peroxide, drive classical microglial activation in the brain. This review examines ROS involvement in neuroinflammation and discusses limitations in current research methods.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Microglia are key immune cells in the central nervous system, crucial for brain development, function, and disease.
- Microglial activation, particularly M1 classical activation, releases pro-inflammatory factors that can worsen brain injury.
- Reactive oxygen species (ROS) are increasingly recognized as critical mediators in microglial activation pathways.
Purpose of the Study:
- To review the role of ROS, specifically hydrogen peroxide from NADPH oxidase, in classical microglial activation.
- To critically assess evidence linking mitochondrial ROS to NLRP3 inflammasome activation and subsequent IL-1β/IL-18 production.
- To discuss the limitations of common experimental techniques used to study ROS in microglial and inflammasome activation.
Main Methods:
- Literature review of studies investigating ROS and microglial activation.
- Critical evaluation of research implicating mitochondrial ROS in NLRP3 inflammasome activation.
- Analysis of limitations associated with ROS detection and inhibition tools (e.g., MitoSOX, MitoTEMPO).
Main Results:
- Evidence strongly links hydrogen peroxide, generated by NADPH oxidase, to classical microglial activation.
- The role of mitochondrial ROS in NLRP3 inflammasome activation remains controversial and requires further investigation.
- Current methods for assessing mitochondrial ROS in microglial activation have significant limitations.
Conclusions:
- ROS, especially hydrogen peroxide, are significant contributors to microglial activation and neuroinflammation.
- Further research is needed to clarify the precise role of mitochondrial ROS in inflammasome activation.
- Improved methodologies are essential for accurately determining the contribution of mitochondrial ROS in neuroinflammatory processes.
