Figure 3.

Schematic of microglial activation in the lysolecithin (LPC) model. Microglia become activated after exposure to LPC itself, and in response to T cells transiently present in the LPC-exposed CNS tissue. Once activated, microglia acquire amoeboid morphology via concurrent activation of non-selective cation channels (1) and KCl cotransporters: non-selective cation channels in the cell body increase osmolarity and cause swelling, while KCl cotransporters in the cell processes reduce osmolarity and cause shrinkage. LPC can also increase intracellular calcium by non-selective transient receptor potential melastatin 2 (TRPM2) (2). Calcium influx in turn activates microglia and calcium-activated K+ channels (3). This results in the release of pro-inflammatory IL1beta in a mechanism independent of P2X7R. Microglia can also release IL1beta via inflammasome activation. Indeed, LPC acts as a DAMP and results in activation of NLRP3 and NLRC4. Activated microglia also release extracellular vesicles with proinflammatory functions early after injection and pro-regenerative effects 7-10 days after injury.