Regeneration of dorsal root axons is related to specific non-neuronal cells lining NGF-treated intraspinal...

The regeneration of sensory axons from severed dorsal roots can be enhanced by the presence of nerve growth factor (NGF)-treated nitrocellulose strips implanted into an intraspinal lesion cavity. Rather than being directly apposed to the transplant, most regenerating axons are separated from the nitrocellulose by several layers of non-neuronal cells, suggesting that these cells may have a role in the promotion of axonal regrowth. The cellular layers associated with untreated nitrocellulose strips or NGF-treated implants were examined in this study to determine if there were differences in their arrangement or orientation along the implant which might explain some of the possible effects of substrate-bound NGF on axonal regrowth. Into a hemisection lesion cavity created in the adult rat lumbar spinal cord NGF-treated or untreated strips of nitrocellulose were placed vertically, with intact pieces of fetal spinal cord (FSC) tissue transplanted along each side. The distal ends of cut dorsal rootlets were apposed to the fetal tissue. Immunocytochemical and electron microscopic examination 30-60 days post-transplantation revealed a distinct layering of cell types along the NGF-treated strips. Closest to the nitrocellulose was a single layer of macrophages, followed by a separate layer of fibroblasts with dense collagen bundles, then a layer of astroglial cells, before reaching the neuropil of the fetal spinal cord tissue. A thickened basal lamina formed between the fibroblast and astrocytic cell layers and bundles of regenerated sensory axons extended along the interface between these two layers. In contrast, non-neuronal cells along untreated nitrocellulose strips were not as well organized, with an intermixing of fibroblasts and astroglial cells and only scattered macrophage-like cells. Axons rarely were found in conjunction with this mixed population of cells and, overall, fewer regenerated axons extended into transplants with untreated nitrocellulose. The results demonstrate consistent differences in the composition and organization of non-neuronal cells adjacent to NGF-treated nitrocellulose implants, compared to untreated implants. This suggests that the presence of bound NGF influences the recruitment of various cells from the surrounding transplant tissue as well as from the previously injured dorsal rootlets. The capacity for NGF to promote the regeneration of sensory axons may be an indirect effect that is mediated or potentiated by the non-neuronal cell population that gathers in response to the presence of bound NGF.