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

Abstract

The ability of a substrate bound neurotrophic factor to promote growth of ascending sensory axons across a complete transection lesion of the rat spinal cord was examined in a transplantation model. Aspiration lesions created a 3 mm long cavity in the upper lumbar spinal cord of adult rats. Five weeks after injury two strips of nerve growth factortreated nitrocellulose, were implanted, each in a medio-lateral position, and apposed to the rostral and caudal surfaces of the cavity. Control animals received untreated nitrocellulose implants. Fetal spinal cord tissue was transplanted alongsideand between these strips. Six weeks post transplantation, animals were sacrificed and vibratome sections through the grafts were processed for immunocytochemical demonstration of ingrowing axons expressing calcitonin gene-related peptide (CGRP-IR), Immunolabeled axons were abundant at the caudal interface between host tissue and the NGF-treated nitrocellulose implants, with dense fascicles of fibers abutting the grafts. As the distance from the caudal surface increased some CGRP-IR fibers extended into the fetal tissue although most appeared to remain oriented in a longitudinal course adjacent to the nitrocellulose. Labeled axons were evident along the entire length of the nitrocellulose and appeared to aggregate at the rostral tip of the implant, with many fibers extending into the host spinal cord rostral to the lesion/transplant site. When untreated nitrocellulose was implanted, fewer labeled axons appeared to extend beyond the caudal host-graft interface. Most CGRP-IR axons displayed limited association or contact with the untreated nitrocellulose in this condition. Computer-assisted quantitative analysis indicated that NGF-treated nitrocellulose supported regrowing host axons for nearly three times the length exhibited by axons associated with non-treated nitrocellulose implants. These results indicate that substrate bound nerve growth factor has the capacity to enhance the regrowth of ascending sensory axons across a traumatic spinal cord injury site. The potential to reestablish functional contacts across such a lesion may be heightened by the ability of neurotrophic factors to promote more extensive axonal regrowth.