Regeneration and remyelination ofXenopus tadpole optic nerve fibres following transection or crush

Abstract

Optic nerves of stage 54-56 Xenopus laevis tadpoles were either transected or crushed, and subsequent Wallerian degeneration, regeneration, and remyelination were examined. After 4 days, normal myelinated fibres were no longer present in the distal stump, and only a few unmyelinated fibres remained. After 10-13 days, the distal nerve consisted mainly of a core of reactive astrocytes with enlarged processes and scattered oligodendrocytes which persisted throughout the degenerative period. Regenerating axons traversed the site of the lesion and extended into the distal stump within 13-15 days. As regeneration progressed, astrocytic processes extended radially from the optic nerve's central cellular core and formed longitudinal compartments for regenerating axons. Between 15-19 days, a few regenerating fibres were remyelinated and by 35 days, more axons were surrounded either by thin collars of oligodendrocyte cytoplasm or by 1-3 spiral turns of myelin membrane. By 95 days, the number of myelinated fibres had increased to about 50% of those present in control nerves. Their myelin sheaths were normal in appearance and thickness relative to their respective axon diameters. The largest axons were surrounded by compact sheaths with 4-9 lamellae.

Regeneration beyond the glial scar

“…Evidence that the glial scar is differentially repulsive depending on the species was demonstrated most convincingly by Reier, who showed that regeneration can occur directly through a glial 'scar' in amphibians 137,138 . In these studies, the optic nerve of Xenopus was repeatedly crushed and the dense reactive glial tissues that were induced were harvested and transplanted near the freshly severed optic stump of a recipient.…”

Axonal interactions with connective tissue and glial substrata during optic nerve regeneration in Xenopus larvae and adults

“…In the amphibian, for example, hypertrophic astrocytes form a scar within the degenerated, central stump of the nerve. In contrast with the inhibitory effect that mammalian astrocytes appear to exert on fiber elongation (e.g., Aguayo et al, 1978;David and Aguayo, 1981; for further discussion, see Kiernan, 1979;Reier et al, in press), this region of gliosis in the amphibian does not impede axonal elongation (Reier and Webster, 1974;Turner and Singer, 1974;Stensaas and Feringa, 1977;Reier, 1979;Scott and Foote, 1981).…”

“…Thus far, most studies of optic nerve regeneration and functional recovery in the fish and amphibian have focused on the interactions between regenerating fibers and their surrounding cellular environment at levels central to a crush or transection site. Only a few, brief descriptions of neuritic elongation through the mesodermal matrix of completely severed optic nerves in these species have been presented (Sperry, 1943;Maturana, 1958;Attardi and Sperry, 1963;Gaze and Jacobson, 1963;Reier and Webster, 1974;Maloney, 1976). In some cases, aberrant axonal outgrowth after opticnerve injury has been observed (Gaze, 1959;Reier ar_d Webster, 1974;Tay and Straznicky, 19801, and the suggestion has been made that physical factors may direct the elongation of axons in peripheral regions of the optic pathway.…”

“…Other investigations have focused on axonal interactions with the surrounding tissue environment that may also contribute to successful regeneration in fish and amphibia. Since the cellular composition of CNS tissue in these species is similar to that of higher vertebrates (e.g., Stensaas, 19771, it has been possible to compare the influences on axonal outgrowth of corresponding cell types in animals that have contrasting regenerative capabilities (Reier and Webster, 1974;Turner and Singer, 1974;Stensaas and Feringa, 1977;Murray, 1976;Lanners and Grafstein, 1980).…”

Functional Recovery and Morphological Changes after Injury to the Optic Nerve

“…Axonal sprouting [3,4], reorganization of con nections [5] or activation of alternative strategies [6] have been considered the neurobiological bases for recovery. In fish and amphibians severed optic axons are able to regen erate and establish new contacts in target tissue [7,8]. However, regeneration of axonal connections in the mam malian optic nerve is usually not seen, except under spe cific experimental conditions [9][10][11], In this case, the mammalian optic nerve behaves similarly to myelinated central nervous fiber bundles [12] and therefore provides an adequate and simple model for studying the effects of central nervous system (CNS) trauma.…”