Chondroitinase treatment enhances axonal regrowth through schwann cell-seeded channels after spinal cord hemisection in adult rats

Abstract

Limited re-entry of axons to the distal host spinal cord is still an intractable knot to intraspinal transplantation attempts at repairing the injured spinal cord. Grafting of Schwann cell-seeded channels into hemisected adult rat spinal cords allowed axonal growth across the graft environment but few axons, if any, could pass through the caudal graft-host interface where intense immunoreactivity for chondroitin sulfate (CS) and glial fibrillary acidic protein was observed. In vitro studies using purified astrocytes further demonstrated CS proteoglycans secreted into the peri-astrocytic environment. We thus hypothesized that the CS glycoforms at regions of reactive gliosis within the caudal graft-host interface contribute to the environmental impediment for axonal growth. To overcome this putative barrier, we attempted to remove the CS moiety by continuous infusion of chondroitinase ABC (Chase) into the distal interface. Chase treatment substantially decreased CS immunoreactivity at the distal interface and increased the number of myelinated axons traversing the graft one month post-treatment as compared to the vehicle-infused controls. BDA anterograde tracing found regenerating axons as far as 5mm into the caudal spinal cord. We conclude that CS produced within the distal graft-host interface is an environmental impediment and that removal of the CS creates a more permissive milieu for axonal regeneration back into the host spinal cord. Supported by HKU 7355/00M, NIH NS36350 & International Spinal Research Trust