Sterile Neuroinflammation and Strategies for Therapeutic Intervention

Figure 2

Response of microglia and astrocytes to the brain injury. DAMPs can signal PRRs expressed in astrocytes and microglia, promoting their activation. Depending on the injury site, severity of brain injury, surrounding environment, and signaling strength, astrocytes and microglia may respond to remove stimulants or to secrete inflammatory mediators. Typically, beneficial activation (M2-like microglia and radial-glia-like astrocytes) is associated with the elevated release of neurotrophic factors, anti-inflammatory cytokines (e.g., IL-4 and IL-10), and enzymes (e.g., arginase 1 and insulin-degrading enzymes) that enhance phagocytic activity. Conversely, detrimental activation of astrocytes and microglia is associated with the elevated and sustained expression of inducible nitric oxide synthase, reactive oxygen species, proinflammatory mediators (e.g., IL-1α/β, IL-6, and TNF), and decreased secretion of neurotrophic factors. These divergent responses may determine whether microglia and astrocytes lead to clear tissue debris or promote chronic neuroinflammation.