Transplantation of sciatic nerve segments into normal and glia-depleted spinal cords

Although peripheral nerves are used as guides in attempts to enhance regeneration in the central nervous system (CNS), surprisingly little is known about the interface that develops between the host tissue and the transplanted or implanted peripheral nerve. This study examines host-nerve interfaces following transplantation of segments of sciatic nerve into the spinal cord under two differing conditions, one in which the spinal cord contains normal numbers of glia and one in which the glial population is reduced. The depletion of the glial population is achieved by exposing the lumbosacral region of the spinal cord in 3-day-old rats to X-rays, a model developed in this laboratory. Twenty days later, segments of fresh or frozen sciatic nerves harvested from other 3-day-old rats were transplanted into the lumbar region of spinal cord in irradiated animals and in their non-irradiated littermate controls. Following a 20-day postoperative period, the interfaces between host spinal cord and sciatic nerves were examined ultrastructurally, and pronounced differences were noted. A distinct scar composed of multiple layers of astrocyte processes completely enveloped the transplant in non-irradiated host spinal cord and confined Schwann cells and fibroblasts to the area enclosed by the scar. Terminals from axons that appeared to have traversed the transplant during this 20-day period ended blindly in the astrocytic scar. In contrast, a complete astrocytic scar failed to form around the transplant in the irradiated, glia-depleted hosts, and Schwann cells intermingled with host tissue. Some Schwann cells migrated away from the transplant, which was placed in the dorsal funiculus, along a perivascular route and extended into the gray matter. In some instances Schwann cells were observed in the ventral gray surrounding blood vessels and motoneurons. From these observations, it is clear that the formation of a distinct astrocytic barrier at the host-graft interface is greatly reduced irradiated host. The effects of astrocyte reduction on enhanced regeneration within the spinal cord are discussed.