Chondroitin sulfate increases around a lesion site after central nervous system injury and is believed to be an impediment to axonal regeneration, because administration of
chondroitinase ABC, a
chondroitin sulfate-degrading
enzyme, promotes axonal regeneration of central neurons. To examine the physiological role of
chondroitin sulfate up-regulation after injury, the nigrostriatal dopaminergic axons were unilaterally transected in mice, and
chondroitinase ABC was then injected into the lesion site. In mice transected only,
tyrosine hydroxylase-immunoreactive axons did not extend across the lesion at 1 or 2 weeks after the transection. Immunoreactivities of
chondroitin sulfate side chains and core
protein of
NG2 proteoglycan increased in and around the lesion site, and a fibrotic
scar containing
type IV collagen deposits developed in the lesion center. In contrast, in mice transected and treated with
chondroitinase ABC, numerous
tyrosine hydroxylase-immunoreactive axons were regenerated across the lesion at 1 and 2 weeks after the transection. In these animals,
chondroitin sulfate immunoreactivity remarkably decreased, and immunoreactivity of 2B6 antibody, which recognizes the stub of degraded
chondroitin sulfate side chains, was enhanced. Furthermore, the formation of a fibrotic
scar and a glia limitans that surrounds the former was completely prevented, although
type IV collagen immunoreactivity remained in newly formed blood capillaries around the lesion site. We discuss the question of whether the
chondroitin sulfate is acting as a direct inhibitor of axonal regeneration or whether the observed changes are due to a prevention of the fibrotic
scar formation and a rearrangement of astrocytic membranes.