title: Roles of chondroitin sulfate and dermatan sulfate in the formation of a lesion scar and axonal regeneration after traumatic injury of the mouse brain.
abstract: 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.
authors: Laboratory of Neural Regeneration, Tokyo Metropolitan Institute of Medical Science, Setagaya City, Tokyo, Japan.
authors: Hong-Peng
authors: HP
authors: Li
authors: Yukari
authors: Y
authors: Komuta
authors: Junko
authors: J
authors: Kimura-Kuroda
authors: Toin H
authors: TH
authors: van Kuppevelt
authors: Hitoshi
authors: H
authors: Kawano
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D001369:Axons / Q000473:pathology / Q000502:physiology*; D001930:Brain Injuries / Q000378:metabolism* / Q000473:pathology; D002809:Chondroitin Sulfates / Q000378:metabolism*; D002921:Cicatrix / Q000378:metabolism*; D018920:Coculture Techniques; D003871:Dermatan Sulfate / Q000378:metabolism*; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009416:Nerve Regeneration / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D003871:Dermatan Sulfate; D002809:Chondroitin Sulfates