Chondroitinase ABC promotes axonal regeneration of Clarke’s neurons across the scar after spinal cord injury

Abstract

The present study examined whether enzymatic digestion of chondroitin sulfate proteoglycan (CSPG) using chondroitinase ABC promoted the regeneration of neurons in Clarke's nucleus (CN) beyond the scar into the rostral spinal cord in neonatal and adult rats. After hemisection of the spinal cord at T11, either vehicle or chondroitinase ABC was applied onto the lesion site. The post-injury survival periods were 2 and 4 weeks. The regenerated CN neurons were retrogradely labeled by Fluoro-Gold injected at spinal cord level C7. In the sham group, injured CN neurons did not regenerate in both neonatal and adult rats. Following treatment with chondroitinase ABC at the lesion site, there were 11.8% and 8.3% of the injured CN neurons regenerated into the rostral spinal cord, 2 and 4 weeks respectively in neonates. In adults, there were 9.4% and 12.3%, 2 and 4 weeks respectively, of the injured CN neurons regenerated their axons to the rostral spinal cord after treatment with chondroitinase ABC. In both neonatal and adult animals, the immunoreactivity for the carbohydrate epitope of CSPG was decreased around the lesion site after treatment with chondroitinase ABC compared to sham control. Our results demonstrate that axonal regeneration in the injured spinal cord can be promoted by degradation of CSPG with chondroitinase ABC. These results further suggest that CSPG is inhibitory to the regeneration of neurons in the spinal cord after traumatic injury. Supported by The Hong Kong Research Grants Council