Bridging a Complete Transection Lesion of Adult Rat Spinal Cord with Growth Factor-Treated Nitrocellulose Implants

摘要

The ability of a substrate boundneurotrophic factor to promote growth ofascending sensory axons across a completetransection lesion of the rat spinal cord wasexamined in a transplantation model. Aspirationlesions created a 3 mm long cavity in the upperlumbar spinal cord of adult rats. Five weeksafter injury two strips of nerve growth factortreatednitrocellulose, were implanted, each in amedio-lateral position, and apposed to therostral and caudal surfaces of the cavity.Control animals received untreated nitrocelluloseimplants. Fetal spinal cord tissue wastransplanted alongsideand between these strips.Six weeks post transplantation, animals weresacrificed and vibratome sections through thegrafts were processed for immunocytochemicaldemonstration of ingrowing axons expressingcalcitonin gene-related peptide (CGRP-IR),Immunolabeled axons were abundant at thecaudal interface between host tissue and theNGF-treated nitrocellulose implants, with densefascicles of fibers abutting the grafts. As thedistance from the caudal surface increased someCGRP-IR fibers extended into the fetal tissuealthough most appeared to remain oriented in alongitudinal course adjacent to the nitrocellulose.Labeled axons were evident along theentire length of the nitrocellulose and appearedto aggregate at the rostral tip of the implant,with many fibers extending into the host spinalcord rostral to the lesion/transplant site. Whenuntreated nitrocellulose was implanted, fewerlabeled axons appeared to extend beyond thecaudal host-graft interface. Most CGRP-IRaxons displayed limited association or contactwith the untreated nitrocellulose in thiscondition. Computer-assisted quantitativeanalysis indicated that NGF-treated nitrocellulosesupported regrowing host axons fornearly three times the length exhibited by axonsassociated with non-treated nitrocelluloseimplants. These results indicate that substratebound nerve growth factor has the capacity toenhance the regrowth of ascending sensoryaxons across a traumatic spinal cord injury site.The potential to reestablish functional contactsacross such a lesion may be heightened by theability of neurotrophic factors to promote moreextensive axonal regrowth.