Dermatan sulfate (DS) is synthesized from
chondroitin sulfate (CS) by epimerization of
glucuronic acid of CS to yield
iduronic acid. In the present study, the role of CS and DS was examined in mice that received transection of nigrostriatal dopaminergic pathway followed by injection of
glycosaminoglycan degrading
enzymes into the lesion site. Two weeks after injury, fibrotic and
glial scars were formed around the lesion, and transected axons did not regenerate beyond the fibrotic
scar. Injection of
chondroitinase ABC (ChABC), which degrades both CS and DS, completely suppressed the fibrotic
scar formation, reduced the
glial scar, and promoted the regeneration of dopaminergic axons. Injection of the DS-degrading
enzyme chondroitinase B (ChB) also yielded similar results. By contrast, injection of
chondroitinase AC (ChAC), a CS-degrading
enzyme, did not suppress the fibrotic and
glial scar formation, but reduced CS immunoreactivity and promoted the axonal regeneration. Addition of transforming growth factor-β1 (TGF-β1) to a co-culture of meningeal fibroblasts and cerebral astrocytes induces a fibrotic
scar-like cell cluster. The effect of TGF-β1 on cluster formation was suppressed by treatment with ChABC or ChB, but not by ChAC. TGF-β1-induced cell cluster repelled neurites of neonatal cerebellar neurons, but addition of ChABC or ChAC suppressed the inhibitory property of clusters on neurite outgrowth. The present study is the first to demonstrate that DS and CS play different functions after
brain injury: DS is involved in the lesion
scar formation, and CS inhibits axonal regeneration.