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. 2022 May 25;323(1):C46–C55. doi: 10.1152/ajpcell.00053.2022

Table 2.

Key mechanisms involving proteoglycans that affect the endothelial glycocalyx, neuroinflammation, and glial scar activity after CNS injury

Mechanism Effects Reference(s)
Endothelial glycocalyx (EG)
 EG heparan sulfate (HS) degradation by multiple mechanisms (see Table 1) Increased blood-brain barrier (BBB) permeability evidenced by increased edema and leukocyte infiltration of brain interstitium (7, 3137, 40)
Neuroinflammation
 HPSE overexpression Attenuates endotoxin-induced neuroinflammation (42)
 Activation of TLR pathway by HSPGs and biglycan Stimulates microglial activation and their production of proinflammatory cytokines TNFα and IL-1β in culture and rodent subarachnoid hemorrhage (SAH) (11, 50, 56, 57)
 Binding of LAR and CD44 by CSPGs Facilitates microglial activation and upregulates their expression of MMPs in vitro (55, 108)
 HS activation of TGF-β Induces microglial activation and increased CSPG production by activated microglia and astrocytes in vitro (52, 53, 109)
Glial scar
 Binding of LAR and RPTPσ by CSPGs Facilitates inhibition of axon growth through several common signaling pathways including Rho/ROCK, mTOR and Erk, as well as distinct effects through cofilin and PKC. Disruption ofcytoskeletal assembly and autophagic flux near growth cones are a few of the downstream effects that inhibit axon regrowth (69, 70, 108)
 Binding of NgR1 and NgR3 by CSPGs Inhibits axon outgrowth presumably by enhancing myelin-associated inhibitor activity through Rho/ROCK mechanisms (70)
 Binding of RPTPσ to HSPGs Competes with CSPGs for the binding domain and promotes axon extension by oligomerizing RPTPσ and inhibiting its downstream effects (70, 86)
 Antagonism of TGF-β by decorin Decreases fibrosis, CSPG expression and promotes neural regeneration both in culture and across in vivo models of TBI, SCI, and SAH (57, 90, 91)

CNS, central nervous system; CSPG, chondroitin sulfate proteoglycan; HSPG, heparan sulfate proteoglycan; LAR, leukocyte common antigen-related phosphatase; MMP, matrix-metalloproteinase; mTOR, mammalian target of rapamycin; SCI, spinal cord injury; TBI, traumatic brain injury; TLR, Toll-like receptor.