Regeneration of central nervous system axons into an acellular tube in the absence of distal tissue

Abstract

To differentiate between local and distant influences on central nerve regeneration, an impervious, stainless-steel cannula, 12 mm long, was placed in the path of severed axons within the corpus callosum of adult rats. The cannula was occluded for 1 week after implantation to prevent herniation of tissue into its lumen. The extracranial end of the tube was plugged with Gelfoam rather than tissue. Inflammatory cells within the tube decreased in number with time and all animals survived for the experiment's duration of 4 to 16 weeks. Some callosal axons grew into the cannula and eventually extended about 1.3 mm. After 8 to 16 weeks, the lumen of the cannula contained many unmyelinated axons, some of which formed fascicles, myelinated axons, demyelinating axons, a few oligodendrocytes, and many astrocytic processes, macrophages, and blood vessels. A striking feature was the linear orientation of cells and their processes. The distal tip of the core resembled a central nervous system explant: it included an appreciable number of growth cones, synaptic terminals embedded in a generous extracellular space, and occasional remyelinating axons. Thus, within an impervious, acellular conduit and in the absence of distal tissue, intrinsic, neuronal processes can be redirected, fasciculate, myelinate, and can regrow alongside glia and endothelium. An indwelling tube, isolating the growth from surrounding brain fluid, may permit assessment of glial, neuronal, and extracellular contributions to the directed regeneration of adult, central axons.