Fig. 3

Roles of astrocytes in remyelination. Reactive astrocytes are induced by cytokines (interleukin [IL]-1α, TNF, and C1q) secreted by activated microglia in response to demyelinating insults. Astrocytes regulate the proliferation, differentiation, and maturation of OPCs by secreting regenerative or inhibitory factors that modulate remyelination. Astrocytes promote OPC proliferation by producing growth factors such as platelet-derived growth factor AA (PDGF-AA), fibroblast growth factor 2 (FGF2), cytokines IL-1β and tumor necrosis factor (TNF), and chemokine C-X-C motif chemokine ligand 1, 8, and 10 (CXCL1, CXCL8, CXCL10). Astrocytes increase OPC differentiation by secreting ciliary neurotrophic factor (CNTF), leukemia inhibitory factor (LIF), insulin-like growth factor-1 (IGF-1), and tissue inhibitor of metalloproteinases-1 (TIMP-1). In contrast, astrocytes also produce inhibitory molecules, such as chondroitin sulfate proteoglycans (CSPGs), endothelin-1 (ET-1), fibronectin, tenascin-c, and jagged-1. Furthermore, astrocytes produce brain-derived neurotrophic factor (BDNF) to promote hyaluronan and fibroblast growth factor 9 (FGF9) to suppress the maturation of OLs