Overcoming the inability of the injured mammalian central nervous system axons to grow into their degenerating environment

Abstract

Spontaneous growth of axons after injury is extremely limited in mammalian central nervous system (CNS). It is now clear, however, that injured CNS axons can elongate, but fail to suitably do so unless their environment is altered. In contrast, goldfish retinal ganglion cells readily regenerate severed axons and make functional connections with their appropriate targets (Attardi and Sperry, 1963). The regenerated axons become myelinated (Murray, 1976) and form a normal pattern of synaptic contacts with their targets (Murray and Edwards, 1982). However, mammalian central neurons have a reduced capacity to regenerate spontaneously after comparable lesions (Grafstein and Ingoglia, 1982; Kiernan, 1979). Optic nerve injury in mammals leads to the death of most of the axotomized neurons, failure of the surviving cells to regrow their axons, and the formation of a dense glial scar at the site of injury (Grafstein and Ingoglia, 1982; Misantone et al., 1984). The ability of the mammalian retinal ganglion cells to survive and regenerate their axons after axotomy can, however, be markedly enhanced by modification of the neuronal environment (Aguayo et al., 1978; Davis et al., 1987; Hadani et al., 1984; Kao et al., 1977; Kromer,1987; Sievers et al., 1987).