FIGURE 1.

Heterogeneity of microglia: phenotypic and functional diversity. In response to disturbance of brain homeostasis like injury or disease, microglia can become polarized toward M1-like and M2-like activation states that can have distinct roles in neurodegeneration and tissue repair. An environment rich with the classical pro-inflammatory stimuli, such as IFN-γ and LPS, promotes the polarization of resting microglia into an M1 phenotype. M1-like microglia are characterized by upregulated expression of phenotypic protein markers such as IL-1β, TNFα, IL-6, and iNOS. They release pro-inflammatory cytokines, chemokines and free radicals that impair brain repair and contribute to chronic neuroinflammation, oxidative stress and long-term neurological impairments. In contrast, a neuroinflammatory environment rich in anti-inflammatory IL-4 or IL-13 drives the development of an M2 phenotype. M2-like microglia upregulate protein markers such as CD206, CD163, FCγR, arginase 1, Ym-1, and TGFβ. M2-like microglia release anti- inflammatory cytokines, neurotrophic factors and proteases, and they have increased phagocytic activity. M2-like microglia promote immunosuppression and resolution of M1-mediated neuroinflammation, and participate in CNS remodeling and repair by modulating neurorestorative processes such as neurogenesis, angiogenesis, oligodendrogenesis and remyelination.