Chondroitin sulphate-derived disaccharides: a potential drug for axons regrowing across the glial scar

Abstract

Chondroitin sulphate (CS) moieties enriched in the glial scar can be cleaved by chondroitinase ABC (ChABC) delivered to the site, resulting in improved outcomes in axonal regrowth and functional recovery. We postulate that the disaccharide products generated during digestion play parts in the enhancement of axonal growth. With a co-culture model of astrocytes and cortical neurons, treated with recombinant ChABC (rChABC) combinations, washed of digestion products and then treated with selected CS disaccharides, neurite growth-promoting effects of CS disaccharides were revealed. By contrast, control treatments with sucrose or CS tetrasaccharides did not promote neurite growth. Among the different CS disaccharides, DdiUA-2S was found superior in the enhancement of neurite growth. Without the pre-treatment of rChABC, the growth-promoting effect was less pronounced and the differences among the CS disaccharides with regard to growthpromoting effects were insignificant. Evidence is thus provided for (1) the role of ChABC activities, in disrupting the barrier to axonal growth, and (2) possible supplementation with the neurite growth-promoting CS disaccharides means to overcome the axonal growth barrier at the glial scar.