Modulators of microglial activation and polarization after intracerebral haemorrhage

• Published in: Nature reviews. Neurology Vol. 13; no. 7; pp. 420 - 433
• Main Authors: Lan, Xi, Han, Xiaoning, Li, Qian, Yang, Qing-Wu, Wang, Jian
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.07.2017; Nature Publishing Group
• Subjects: 13/100; 631/250/2504/342/1952; 64/60; 64/86; 692/308/575; 692/617/375/534; 692/699/75/593/1370; Animals; Astrocytes - immunology; Astrocytes - metabolism; Brain research; Cerebral Hemorrhage - immunology; Cerebral Hemorrhage - metabolism; Cytokines - immunology; Cytokines - metabolism; Hemorrhage; Humans; Intracerebral hemorrhage; Medicine & Public Health; Microglia; Microglia - immunology; Microglia - metabolism; Neurology; Oligodendroglia - immunology; Oligodendroglia - metabolism; Patient outcomes; Physiological aspects; review-article; T-Lymphocytes - immunology; T-Lymphocytes - metabolism
• ISSN: 1759-4758; 1759-4766; 1759-4766
• DOI: 10.1038/nrneurol.2017.69

Key Points Microglial polarization after intracerebral haemorrhage (ICH) modulates microglial phagocytic function and might affect haematoma clearance Activation of microglia to an M1-like phenotype occurs mainly in the acute phase after ICH M2-like microglial responses occur in the subacute and chronic phase and might contribute to phagocytosis of cell debris and haematoma clearance Microglial polarization can be regulated by transcription factors, chemokines, receptors and their signalling pathways, and interactions between microglia and other cells in the brain (T lymphocytes, neurons, astrocytes and oligodendrocytes) Data from clinical trials and preclinical studies suggest that targeting of microglial phenotype switching represents a new research direction for ICH treatment Effective drug treatments for intracerebral haemorrhage (ICH) are still lacking. However, therapies that target microglial phenotype switching might soon become available for affected patients. Here, Wang and colleagues summarize key advances in understanding of microglial function after ICH, including modulators of microglial function and interactions with other cells. 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.