Microglial and macrophage polarization-new prospects for brain repair

Nat Rev Neurol, 2015 · DOI: 10.1038/nrneurol.2014.207 · Published: January 1, 2015

Simple Explanation

Microglia and macrophages, key immune cells in the brain, can either help or hinder recovery after brain injury. This depends on which 'phenotype' or activation state they adopt. M1 microglia/macrophages are generally pro-inflammatory and can worsen damage, while M2 microglia/macrophages promote tissue repair and regeneration. Future therapies should aim to carefully control the balance between M1 and M2 phenotypes to maximize brain repair after injury, rather than simply suppressing all microglia/macrophages.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Level 5 Review

Key Findings

1
Microglia/macrophages exhibit a dynamic shift in phenotype after CNS injury, with an initial M2-dominant phase followed by a later M1-dominant phase.
2
M2 microglia/macrophages promote restorative processes such as neurogenesis, axonal remodeling, angiogenesis, oligodendrogenesis, and remyelination.
3
Extracellular signals (e.g., cytokines, matrix proteins) and intracellular molecular switches (e.g., STATs, PPAR-γ, miRNAs) regulate microglia/macrophage phenotype.

Research Summary

Microglia/macrophages are double-edged swords in the battle for neurological recovery. On the one hand, microglia/macrophage activation fosters brain recovery by clearing cell debris, resolving local inflammation, and releasing a plethora of trophic factors. M2 phenotype is known to promote restorative processes, including neurogenesis, axonal remodeling, angiogenesis, oligodendrogenesis, and remyelination. Recent findings on regulatory molecules that control phenotype switching, including extracellular stimulating factors and intracellular signaling molecules may accelerate the pace of research towards that goal.

Practical Implications

Therapeutic Target

Targeting microglia/macrophage polarization could be a novel therapeutic approach for CNS remodeling.

Cell-based regenerative strategy

Transplantation of ex vivo activated M2 cells to counteract the M2-to-M1 shift at late stages of injuries is a promising cell-based regenerative strategy.

Molecular Targets

Extracellular signals and intracellular molecular switches that control phenotypic changes provide two promising methods for microglia/macrophage-targeted regenerative therapy.

Study Limitations

1
Our picture of microglia/macrophage phenotypes is still incomplete.
2
The action of many phenotype inducers is not a simple all-or-none phenomenon, but a function of timing and dose.
3
Most of our knowledge on microglia/macrophage polarization is derived from rodents and there are many differences between rodent microglia/macrophages and their human counterparts.

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