Immediate elimination of injured white matter tissue achieves a rapid axonal growth across the severed spinal cord in adult rats

Abstract

In general, axonal regeneration is very limited after transection of adult rat spinal cord. We previously demonstrated that regenerative axons reached the lesion site within 6h of sharp transection with a thin scalpel. However, they failed to grow across the lesion site, where injured axon fragments (axon-glial complex, AGC) were accumulated. Considering a possible role of these axon fragments as physicochemical barriers, we examined the effects of prompt elimination of the barriers on axonal growth beyond the lesion site. In this study, we made additional oblique section immediately after the primary transection and surgically eliminated the AGC (debridement). Under this treatment, regenerative axons successfully traversed the lesion site within 4h of surgery. To exclude axonal sparing, we further inserted a pored sheet into the debrided lesion and observed the presence of fascicles of unmyelinated axons traversing the sheet through the pores by electron microscopy, indicating bona fide regeneration. These results suggest that the sequential trial of reduction and early elimination of the physicochemical barriers is one of the effective approaches to induce spontaneous and rapid regeneration beyond the lesion site.