Regeneration of spinal neurons in inframammalian vertebrates: morphological and developmental aspects

This review discusses regeneration of spinal neurons in inframammalian vertebrates. In contrast to the limited regeneration of nerve fibers in mammalian spinal cord, relatively complete regeneration of spinal cord, including the formation of new neurons, occurs in cyclostomes, selachians, teleosts, and urodele amphibians. The various experimental techniques which have been used to accelerate or enhance regeneration of spinal cord, such as implantation of peripheral nerve bridges, application of growth factors or chemical agents, and the application of exogenous electrical fields, are discussed. Processes involved in regeneration of other systems, e.g., the trophic effect of nerve fibers, the effect of certain hormones, and the effects of the blastema, are discussed as they may relate to regeneration in the spinal cord. Recent work on the factors which influence nerve outgrowth is discussed. Factors such as diffusible chemical gradients, contact with other cells, pre-formed channels for nerve growth, and differences in adhesivity of neurites for the substratum may act to control the direction of axon outgrowth in regeneration as well as normal embryonic development. This article next reviews work from our laboratory on regeneration of spinal neurons in the teleost, Sternarchus albifrons. We have used Sternarchus as a model system for the study of regeneration and remyelination since: 1. spinal cord readily regenerates after amputation of the tail, 2. new nerve cell bodies are formed during this regeneration, and 3. Sternarchus contains large neurogenic electric organs which also regenerate after tail amputation. The axons of the electric organ arise from spinal neurons and have a highly specific and complex morphology which is recapitulated after regeneration. Studies on Sternarchus indicate that new nerve cell bodies are produced during regeneration from the enlarged ependymal cells. Initially, many more of the electromotor neurons are produced in regenerated spinal cord than are present normally. Cell death subsequently occurs in some of these asynaptic cells, reducing the number of electrocytes in older regenerated cord to a more normal condition. The spinal electromotor neurons in Sternarchus have also been used to demonstrate that section of the axon in an asynaptic neuron will produce a typical "axon reaction" in the cell body. It is interesting that cell death during regeneration and the retrograde axon reaction both appear to occur without loss of synaptic elements in these normally asynaptic cells. Neurites grow through regenerating Sternarchus spinal cord in small bundles, in close contact with adjacent ependymal cell processes. Longitudinal channels, filled with neurites, are seen extending through many stages of regenerating Sternarchus cord, usually near the periphery of the cord. There are numerous invaginations of the peripheral edge of regenerating cord and its associated external lamina. These infoldings may be involved in the generation of the neurite filled channels.(ABSTRACT TRUNCATED AT 400 WORDS)