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Updated: Mar 2, 2026
Three-dimensional Confocal Analysis of Microglia/macrophage Markers of Polarization in Experimental Brain Injury
Published on: September 4, 2013
Modulators of microglial activation and polarization after intracerebral haemorrhage
Xi Lan1, Xiaoning Han1, Qian Li1
1Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Ross Building 370B, Baltimore, Maryland 21205, USA.
Abstract:
Intracerebral haemorrhage (ICH) is the most lethal subtype of stroke but currently lacks effective treatment. Microglia are among the first non-neuronal cells on the scene during the innate immune response to ICH. Microglia respond to acute brain injury by becoming activated and developing classic M1-like (proinflammatory) or alternative M2-like (anti-inflammatory) phenotypes. This polarization implies as yet unrecognized actions of microglia in ICH pathology and recovery, perhaps involving microglial production of proinflammatory or anti-inflammatory cytokines and chemokines. Furthermore, alternatively activated M2-like microglia might promote phagocytosis of red blood cells and tissue debris, a major contribution to haematoma clearance. Interactions between microglia and other cells modulate microglial activation and function, and are also important in ICH pathology. This Review summarizes key studies on modulators of microglial activation and polarization after ICH, including M1-like and M2-like microglial phenotype markers, transcription factors and key signalling pathways. Microglial phagocytosis, haematoma resolution, and the potential crosstalk between microglia and T lymphocytes, neurons, astrocytes, and oligodendrocytes in the ICH brain are described. Finally, the clinical and translational implications of microglial polarization in ICH are presented, including the evidence that therapeutic approaches aimed at modulating microglial function might mitigate ICH injury and improve brain repair.
Insights
Intracerebral haemorrhage (ICH) lacks effective treatments. This review explores how microglia, immune cells in the brain, polarize into M1 or M2 phenotypes, influencing ICH pathology and recovery, offering therapeutic potential.
Area of Science:
- Neuroscience
- Immunology
- Pathology
Background:
- Intracerebral haemorrhage (ICH) is a severe stroke subtype with limited therapeutic options.
- Microglia are key innate immune cells responding to brain injury, exhibiting proinflammatory (M1) and anti-inflammatory (M2) phenotypes.
- Microglial polarization is implicated in ICH pathogenesis and resolution, involving cytokine production and phagocytosis.
Purpose of the Study:
- To review the role of microglial activation and polarization in intracerebral haemorrhage.
- To summarize modulators, markers, and signaling pathways of microglial phenotypes in ICH.
- To discuss the clinical implications of targeting microglial function for ICH treatment.
Main Methods:
- Literature review of studies on microglial response to ICH.
- Analysis of M1/M2 microglial phenotypes, including markers and transcription factors.
- Examination of cell-cell interactions and their impact on microglial function in ICH.
Main Results:
- Microglial polarization into M1 (proinflammatory) and M2 (anti-inflammatory) phenotypes significantly impacts ICH.
- M2 microglia may enhance haematoma clearance through phagocytosis of blood components and debris.
- Interactions with neurons, astrocytes, and oligodendrocytes modulate microglial activity in the ICH environment.
Conclusions:
- Microglial polarization is a critical factor in ICH pathology and recovery.
- Targeting microglial phenotypes presents a promising therapeutic strategy for mitigating ICH injury.
- Further research into microglial modulation could lead to improved clinical outcomes for ICH patients.
