Fig. 3.

A schematic summary showing the mechanisms by which astroglial TLRs contribute to CNS injury. Following TBI and SCI, cells and tissue at the affected site are progressively damaged. Stressed and necrotic cells release endogenous TLR ligands. HMGB1 activates TLR2 and TLR4, mRNA stimulates TLR3, and mtDNA promotes TLR9 signaling, respectively. This leads to the production of pro-inflammatory mediators, which further exacerbate the tissue damage and neuroinflammation. In addition, the activation of astroglial TLR4 enhances the expression of AQP4 and astrocyte swelling by mechanisms that remain elusive. Moreover, TLR9 is involved in the modulation of astrocyte proliferation in SCI.