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

Abstract

Introduction: We have previously shown that enzymatic digestion of chondroitin sulfate proteoglycan (CSPG) at the injury scar promotes the axonal regeneration of Clarke’s nucleus (CN) neurons into an peripheral nerve graft after spinal cord hemisection. The present study examined whether digestion of CSPG using chondroitinase ABC promoted the regeneration of CN neurons across the scar into the rostral spinal cord in neonatal and adult rats. Method: Following hemisection of the spinal cord at T11, either vehicle or chondroitinase ABC was applied onto the lesion site. The postoperative survival periods were 2 and 4 weeks. Regenerating CN neurons were retrogradely labeled by Fluoro-Gold injection at spinal cord level C7. Results: In the sham group, there was no regeneration of injured CN neurons in both neonatal and adult rats. Treatment with chondroitinase ABC in neonates resulted in 11.8% and 8.3% of the injured CN neurons regenerated into the rostral spinal cord, 2 and 4 weeks respectively. 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 chondroitinase ABC treatment, the immunoreactivity for CSPG was dramatically decreased around the lesion site in both neonatal and adult animals. Conclusion: Our results show that degradation of CSPG with chondroitinase ABC can promote the axonal regeneration in the spinal cord. These results further support the hypothesis that CSPG is inhibitory to the regeneration of neurons in the spinal cord after traumatic injury. Acknowledgement: This work was supported by grants from the Hong Kong Research Grants Council and the University of Hong Kong.