Fig. 1

The neuroinflammatory response. Upon infection, insult, or injury to brain tissue and/or organelles, resting microglia are stimulated by PAMPs, DAMPs, reactive oxygen species (ROS), and cytokines. Activated microglia exist along a spectrum of pro-inflammatory (M1-like; neurotoxic) and anti-inflammatory (M2-like; neuroprotective) states, where pro-inflammatory cytokines (i.e., IL-1β, IL6, TNF), reactive oxygen species (ROS), free radicals (NO), and anti-inflammatory cytokines (i.e., TGFB, IL4, IL10, IL13) inform various neurotoxic and/or neuroprotective pathways. Pro-inflammatory cytokines, particularly IL-1β, can activate the NLRP3 inflammasome, which further modulates neurotoxic pathways. Cytokine release is also a means by which microglia communicate with one another and with astrocytes. Resting astrocytes are activated through such cellular communication with microglia, and exist as either A1 (pro-inflammatory) or A2 (anti-inflammatory) astrocytes, where cytokine release can cross-talk with microglia and further activate neurotoxic or neuroprotective pathways