Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2022 Nov 3:9:1034692.
doi: 10.3389/fmed.2022.1034692. eCollection 2022.

Therapeutic targeting of microglia mediated oxidative stress after neurotrauma

Austin N Smith  1   2 , Michael Shaughness  1   2 , Sean Collier  2   3 , Deanna Hopkins  2   3 , Kimberly R Byrnes  1   3
Affiliations
Review

Therapeutic targeting of microglia mediated oxidative stress after neurotrauma

Austin N Smith et al. Front Med (Lausanne). .

Abstract

Inflammation is a primary component of the central nervous system injury response. Traumatic brain and spinal cord injury are characterized by a pronounced microglial response to damage, including alterations in microglial morphology and increased production of reactive oxygen species (ROS). The acute activity of microglia may be beneficial to recovery, but continued inflammation and ROS production is deleterious to the health and function of other cells. Microglial nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX), mitochondria, and changes in iron levels are three of the most common sources of ROS. All three play a significant role in post-traumatic brain and spinal cord injury ROS production and the resultant oxidative stress. This review will evaluate the current state of therapeutics used to target these avenues of microglia-mediated oxidative stress after injury and suggest avenues for future research.

Keywords: NADPH oxidase; iron; microglia; mitochondria; oxidative stress; spinal cord injury; traumatic brain injury.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Microglia mediated oxidative stress leads to neurotoxicity.
FIGURE 2
FIGURE 2
Oxidative stress in microglia. Microglia can produce reactive oxygen species (ROS) through NOX2, mitochondrial oxidative phosphorylation, and the Fenton reaction with iron. ROS act as signaling molecules to mediate pathways pivotal in microglial functions.
FIGURE 3
FIGURE 3
Reactive oxygen species in microglia. NOX2, the primary reactive oxygen species (ROS)-generating enzyme in microglia, produces superoxide. Superoxide dismutase then catalyzes the dismutation of superoxide to produce hydrogen peroxide. Iron reacts with hydrogen peroxide, generating hydroxyl radicals.
See this image and copyright information in PMC

References

    1. Nscisc. National spinal cord injury statistical center, facts and figures at a glance. Birmingham, Al: University of Alabama at Birmingham; (2016).
    1. Chaychi S, Valera E, Tartaglia MC. Sex and gender differences in mild traumatic brain injury/concussion. Int Rev Neurobiol. (2022) 164:349–75. 10.1016/bs.irn.2022.07.004 - DOI - PubMed
    1. Lindberg MA, Moy Martin EM, Marion DW. Military traumatic brain injury: The history, impact, and future. J Neurotrauma. (2022) 39:1133–45. 10.1089/neu.2022.0103 - DOI - PMC - PubMed
    1. Kumar A, Alvarez-Croda DM, Stoica BA, Faden AI, Loane DJ. Microglial/macrophage polarization dynamics following traumatic brain injury. J Neurotrauma. (2015) 33:1732–50. - PMC - PubMed
    1. Loane DJ, Byrnes KR. Role of microglia in neurotrauma. Neurotherapeutics. (2010) 7:366–77. 10.1016/j.nurt.2010.07.002 - DOI - PMC - PubMed

LinkOut - more resources