Microglia, Brain Inflammation, and White Matter Repair – Summary

By SWA

Microglia are the central nervous system’s resident immune cells, acting as first responders to injury, infection, and disease. They play vital roles in brain development, immune defense, tissue repair, and maintenance of neural circuits.

1. Role in White Matter Repair
Microglia can contribute to white matter restoration by:

  • Clearing inhibitory myelin debris after injury.

  • Supporting oligodendrocyte precursor cell (OPC) proliferation and differentiation.
    However, complete regeneration of lost white matter depends on multiple factors, and microglia alone may not be sufficient.

2. Functions in Brain Health

  • Immune surveillance – Constantly monitor the brain’s microenvironment for damage or pathogens.

  • Phagocytosis – Remove debris, misfolded proteins, and dying cells.

  • Neuroinflammation – Produce cytokines and other inflammatory mediators; beneficial for defense but harmful if chronic.

  • Developmental roles – Prune synapses, refine neural circuits, and promote myelination.

  • Tissue repair – Release growth factors, promote regeneration, and restore homeostasis.

3. Mechanisms of Microglial Damage and Dysfunction

  • Chronic activation (reactive microgliosis) – Prolonged inflammation can become neurotoxic, releasing harmful cytokines (TNF-α, IL-1β) and ROS.

  • Oxidative stress – Excess ROS can damage both microglia and surrounding neurons.

  • Debris overload – Failure to degrade cellular waste can perpetuate inflammation, as in Alzheimer’s disease.

  • Aging – Older microglia are more prone to dysfunction and inflammatory bias.

  • Immune cell infiltration – Peripheral immune cells can worsen inflammation and harm microglia.

4. Pathogen-Induced Microglial Damage

  • Viruses (e.g., HIV, SARS-CoV-2, herpes) – Can directly infect or chronically activate microglia, leading to persistent neuroinflammation.

  • Bacteria – Trigger strong inflammatory responses that can protect against infection but also injure neurons.

  • Fungi (e.g., Cryptococcus) – May evade destruction by living within microglia, causing prolonged immune stress.

5. Implications for Disease
Dysfunctional or chronically activated microglia contribute to neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and multiple sclerosis. Targeting microglial pathways may offer therapeutic potential for controlling harmful inflammation while preserving repair functions.

 Note:
Microglia can damage DNA, and this DNA damage can trigger inflammatory responses in the brain. A deficiency of certain enzymes, such as DNase II, in microglia can lead to the accumulation of DNA fragments, which in turn promotes inflammation. These inflammatory responses can be detected by elevated levels of inflammatory cytokines such as IL-6, TNF-α, and IL-1β.

Microglial double stranded DNA accumulation induced by DNase II deficiency drives neuroinflammation and neurodegeneration
https://jneuroinflammation.biomedcentral.com/articles/10.1186/s12974-025-03333-6

Read extended version and references:
https://swaresearch.blogspot.com/2025/08/microglia-and-brain-inflammation.html

References:

Microglia to the Rescue
https://www.science.org/content/blog-post/microglia-rescue

CSF1R-related leukoencephalopathy
https://pmc.ncbi.nlm.nih.gov/articles/PMC6329328/

 

© 2000-2025 Sieglinde W. Alexander. All writings by Sieglinde W. Alexander have a fife year copy right. Library of Congress Card Number: LCN 00-192742


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