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Regeneration of adult rat CNS axons into peripheral nerve autografts: ultrastructural studies of the early stages of axonal sprouting and regenerative axonal growth

  • Published:
Journal of Neurocytology

Summary

If one end of a segment of peripheral nerve is inserted into the brain or spinal cord, neuronal perikarya in the vicinity of the graft tip can be labelled with retrogradely transported tracers applied to the distal end of the graft several weeks later, showing that CNS axons can regenerate into and along such grafts. We have used transmission EM to examine some of the cellular responses that underlie this regenerative phenomenon, particularly its early stages. Segments of autologous peroneal or tibial nerve were inserted vertically into the thalamus of anaesthetized adult albino rats. The distal end of the graft was left beneath the scalp. Between five days and two months later the animals were killed and the brains prepared for ultrastructural study. Semi-thin and thin sections through the graft and surrounding brain were examined at two levels 6–7 mm apart in all animals: close to the tip of the graft in the thalamus (proximal graft) and at the top of the cerebral cortex (distal graft). In another series of animals with similar grafts, horseradish peroxidase was applied to the distal end of the graft 24–48 h before death. Examination by LM of appropriately processed serial coronal sections of the brains from these animals confirmed that up to several hundred neurons were retrogradely labelled in the thalamus, particularly in the thalamic reticular nucleus.

Between five and 14 days after grafting, large numbers of tiny (0.05–0.20 μm diameter) nonmyelinated axonal profiles, considered to be axonal sprouts, were observed by EM within the narrow zone of abnormal thalamic parenchyma bordering the graft. The sprouts were much more numerous (commonly in large fascicles), smoother surfaced, and more rounded than nonmyelinated axons further from the graft or in corresponding areas on the contralateral side of animals with implants or in normal animals. At longer post-graft survival times, the number of such axons in the parenchyma around the graft declined.

At five days, some axonal sprouts had entered the junctional zone between the brain and the graft. By eight days there were many sprouts in the junctional zone and some had penetrated the proximal graft to lie between its basal lamina-enclosed columns of Schwann cells, macrophages and myelin debris. Within the brain, sprouts were in contact predominantly with other sprouts but also with all types of glial cell. Within the junctional zone and graft many sprouts showed no consistent, close associations with other cell processes, although some were in contact or adjacent to processes of astrocytes, Schwann cells or macrophages. There was no evidence to suggest that axonal sprouts grew along astrocytic extensions to reach the junctional zone and graft. At eight days many axons in the junctional zone and graft were in contact with Schwann cell processes. Such axons, particularly those in intimate contact with the Schwann cell, were larger than those which had not established contact. By 14 days, most axons in the proximal graft were surrounded by Schwann cell processes, predominantly in basal lamina-enclosed columns. Some axons were associated with astrocyte processes, either in basal lamina-enclosed columns containing only astrocyte processes and axons or in columns containing a mixture of astrocyte and Schwann cell processes. The astrocyte processes involved in such bundles were concentrated at the periphery of the proximal graft, were not seen in the distal graft and probably represent long finger-like extensions of the astrocytes which rapidly form a glia limitans at the interface between brain and graft. This glia limitans was partially constructed at five days, almost complete at 14 days and subsequently became progressively thicker and more complex.

At one month the proximal graft had acquired many of the features of a regenerating peripheral nerve and axons were present in large numbers in the distal graft. However the axon-Schwann cell relationships were immature in many of the Schwann cell columns both proximally and distally at one month, and virtually no myelination was apparent. At two months there were numerous myelinated fibres both proximally and distally although there were larger numbers of nonmyelinated axons, many in immature relationship with associated Schwann cells. Thus the graft appears to offer not only support for axonal elongation but also for a substantial degree of maturation of at least some of the regenerating axons, although (as will be reported elsewhere), the regenerated nerve fibres began to regress after two months.

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References

  • Aguayo, A. J. (1985) Axonal regeneration from injured neurons in the adult mammalian central nervous system. InSynaptic Plasticity (edited byCotman, C. W.), pp. 457–84. New York: The Guilford Press.

    Google Scholar 

  • Aguayo, A. J., Charron, L. &Bray, G. M. (1976) Potential of Schwann cells from unmyelinated nerves to produce myelin: a quantitative ultrastructural and autoradiographic study.Journal of Neurocytology 5, 565–73.

    Google Scholar 

  • Aguayo, A. J., Bray, G. M., Rasminsky, M., Zwimpfer, T., Carter, D. &Vidal-Sanz, M. (1990) Synaptic connections made by axons regenerating in the central nervous system of adult mammals.Journal of Experimental Biology 153, 199–224.

    Google Scholar 

  • Ahmed, A. M. &Weller, R. O. (1979) The blood-nerve barrier and reconstitution of the perineurium following nerve grafting.Neuropathology and Applied Neurobiology 5, 469–83.

    Google Scholar 

  • Anderson, P. N., &Turmaine, M. (1986) Peripheral nerve regeneration through grafts of living and freeze-dried CNS tissue.Neuropathology and Applied Neurobiology 12, 389–99.

    Google Scholar 

  • Anderson, P. M., Mitchell, J., Mayor, D. &Stauber, V. V. (1983) An ultrastructural study of the early stages of axonal regeneration through rat nerve grafts.Neuropathology and Applied Neurobiology 9, 455–66.

    Google Scholar 

  • Anderson, P. N., Woodham, P. &Turmaine, M. (1989) Peripheral nerve regeneration through optic nerve grafts.Acta Neuropathologica 77, 525–34.

    Google Scholar 

  • Andres, K-H., Von Düring, M., Muszynski, K. &Schmidt, R. F. (1987) Nerve fibres and their terminals of the dura mater encephali of the rat.Anatomy and Embryology 175, 289–301.

    Google Scholar 

  • Benfey, M. &Aguayo, A. J. (1982) Extensive elongation of axons from rat brain into peripheral nerve grafts.Nature 296, 150–2.

    Google Scholar 

  • Benfey, M., Bünger, U., Vidal-Sanz, M., Bray, G. M. &Aguayo, A. J. (1985) Axonal regeneration from GABAergic neurons in the adult rat thalamus.Journal of Neurocytology 14, 279–96.

    Google Scholar 

  • Benowitz, L. I. &Routtenberg, A. (1987) A membrane phosphoprotein associated with neural development, axonal regeneration, phospholipid metabolism and synaptic plasticity.Trends in Neurosciences 10, 527–32.

    Google Scholar 

  • Berry, M., Rees, L. &Sievers, J. (1986) Unequivocal regeneration of rat optic nerve axons into sciatic nerve isografts. InNeural Transplantation and Regeneration (edited byDas, G. D. &Wallace, R. B.), pp. 63–79. New York: Springer-Verlag.

    Google Scholar 

  • Berry, M., Hall, S., Follows, R., Rees, L., Gregson, N. &Sievers, J. (1988a) Response of axons and glia at the site of anastomosis between the optic nerve and cellular or acellular sciatic nerve grafts.Journal of Neurocytology 17, 727–44.

    Google Scholar 

  • Berry, M., Rees, L., Hall, S., Yiu, P. &Sievers, J. (1988b) Optic axons regenerate into sciatic nerve isografts only in the presence of Schwann cells.Brain Research Bulletin 20, 223–31.

    Google Scholar 

  • Blakemore, W. F. (1976) Invasion of Schwann cells into the spinal cord of the rat following local injections of lysolecithin.Neuropathology and Applied Neurobiology 2, 21–39.

    Google Scholar 

  • Blakemore, W. F., Crang, A. J. &Curtis, R. (1986) The interaction of Schwann cells with CNS axons in regions containing normal astrocytes.Acta Neuropathologica 71, 295–300.

    Google Scholar 

  • Bray, G. M. &Aguayo, A. J. (1989) Exploring the capacity of CNS neurons to survive injury, regrow axons, and form new synapses in adult mammals. InNeural Regeneration and Transplantation pp. 67–78. Alan R. Liss, Inc.

  • Bunge, R. P. (1986) The cell of Schwann. InDiseases of the Nervous System (edited byAsbury, A. K., McKhann, G. M. &McDonald, W. I.), pp. 153–62. Philadelphia: Saunders.

    Google Scholar 

  • Campbell, G. &Frost, D. O. (1988) Synaptic organization of anomalous retinal projections to the somatosensory and auditory thalamus: target-controlled morphogenesis of axon terminals and synaptic glomeruli.Journal of Comparative Neurology 272, 383–408.

    Google Scholar 

  • Campbell, G., So, K-F. &Lieberman, A. R. (1984) Normal postnatal development of retinogeniculate axons and terminals and identification of inappropriately-located transient synapses.Neuroscience 13, 743–59.

    Google Scholar 

  • Campbell, G., Anderson, P. N., Turmaine, M. &Lieberman, A. R. (1989a) Peripheral nerve grafts in the thalamus of the adult rat: ultrastructure of the graft/brain interface.Neuroscience Letters Supplement 36, S93.

    Google Scholar 

  • Campbell, G., Anderson, P. N., Turmaine, M. &Lieberman, A. R. (1989b) Early stages of regenerative growth of adult CNS axons into peripheral nerve grafts.Society for Neuroscience Abstracts 15, 883.

    Google Scholar 

  • Campbell, G., Lieberman, A. R., Anderson, P. N. &Turmaine, M. (1990) Axonal sprouting in the thalamus of adult rats following implantation of a peripheral nerve graft.Journal of Anatomy 170, 229–30.

    Google Scholar 

  • Campbell, G., Anderson, P. N., Turmaine, M. &Lieberman, A. R. (1991) GAP-43 in the axons of mammalian CNS neurons regenerating into peripheral nerve grafts.Experimental Brain Research 87, 67–74.

    Google Scholar 

  • Campbell, G., Vaudano, E., Davies, A. P., Anderson, P. N., Lieberman, A. R. &Schreyer, D. J. (1992) GAP-43 and NGF-receptor expression in adult rat thalamus after injury or peripheral nerve implantation.Society for Neuroscience Abstracts, in press.

  • Carmignoto, G., Comelli, M. C., Candeo, P., Cavicchioli, L., Yan, Q., Merighi, A. &Maffei, L. (1991) Expression of NGF receptor and NGF receptor mRNA in the developing and adult rat retina.Experimental Neurology 111, 302–11.

    Google Scholar 

  • Carter, D. A., Bray, G. M. &Aguayo, A. J. (1989) Regenerated retinal ganglion cell axons can form welldifferentiated synapses in the superior colliculus of adult hamsters.Journal of Neuroscience 9, 4042–50.

    Google Scholar 

  • Chi, N. H., &Dahl, D. (1983) Autologous peripheral nerve grafting into murine brain as a model for studies of regeneration in the central nervous system.Experimental Neurology 79, 245–64.

    Google Scholar 

  • Chi, N. H., Bignami, A., Bich, N. T. &Dahl, D. (1980) Autologous sciatic nerve graft to the rat spinal cord: immunofluorescence studies with neurofilament and gliofilament (GFA) antisera.Experimental Neurology 68, 568–80.

    Google Scholar 

  • Cho, E. Y. P. &So, K-F. (1987) Rate of regrowth of damaged retinal ganglion cell axons regenerating in a peripheral nerve graft in adult hamsters.Brain Research 419, 369–74.

    Google Scholar 

  • Cho, E. Y. P. &So, K-F. (1989) De novo formation of axon-like processes from axotomized retinal ganglion cells which exhibit long distance growth in a peripheral nerve graft in adult hamsters.Brain Research 484, 371–7.

    Google Scholar 

  • Cho, E. Y. P. &So, K-F. (1992) Characterisation of the sprouting response of axon-like processes from retinal ganglion cells after axotomy in adult hamsters: a model using intravitreal implantation of a peripheral nerve.Journal of Neurocytology 21, 589–603.

    Google Scholar 

  • Grain, B. J. &Hall, W. C. (1980) The normal organization of the lateral posterior nucleus of the golden hamster.Journal of Comparative Neurology 193, 351–70.

    Google Scholar 

  • Curtis, R., Stewart, H. J. S., Hall, S. M., Wilkin, G. P., Mirsky, R. &Jessen, K. R. (1992) GAP-43 is expressed by nonmyelin-forming Schwann cells of the peripheral nervous system.Journal of Cell Biology 116, 1455–64.

    Google Scholar 

  • Cunningham, T. J., Haun, F. &Chantler, P. D. (1987) Diffusible proteins prolong survival of dorsal lateral geniculate neurons following occipital cortex lesions in newborn rats.Developmental Brain Research 37, 133–41.

    Google Scholar 

  • Da Cunha, A. &Vitkovic, L. (1990) Regulation of immunoreactive GAP-43 expression in rat cortical macroglia is cell type specific.Journal of Cell Biology 111, 209–15.

    Google Scholar 

  • David, S. &Aguayo, A. J. (1981) Axonal elongation into peripheral nervous system ‘bridges’ after central nervous system injury in adult rats.Science 214, 931–3.

    Google Scholar 

  • Dyson, S. E., Harvey, A. R., Trapp, B. D. &Heath, J. W. (1988) Ultrastructural and immunohistochemical analysis of axonal regrowth and myelination in membranes which form over lesion sites in the rat visual system.Journal of Neurocytology 17, 797–808.

    Google Scholar 

  • Eckenstein, F. P., Shipley, G. D. &Nishi, R. (1991) Acidic and basic fibroblast growth factors in the nervous system: distribution and differential alteration of levels after injury of central versus peripheral nerve.Journal of Neuroscience 11, 412–19.

    Google Scholar 

  • Friedman, B. &Aguayo, A. J. (1985) Injured neurons in the olfactory bulb of the adult rat grow axons along grafts of peripheral nerve.Journal of Neuroscience 5, 1616–25.

    Google Scholar 

  • Gauthier, P. &Rasminsky, M. (1988) Activity of medullary respiratory neurons regenerating axons into peripheral nerve grafts in the adult rat.Brain Research 438, 225–36.

    Google Scholar 

  • Gilmore, S. A. (1973) Long term effects of ionising radiation on rat spinal cord: Intramedullary connective tissue formation.American Journal of Anatomy 137, 1–18.

    Google Scholar 

  • Gilmore, S. A. &Duncan, D. (1968) On the presence of peripheral-like neurones and connective tissue within irradiated spinal cord.Anatomical Record 160, 675–90.

    Google Scholar 

  • Hagg, T., Vahlsing, H. L., Manthorpe, M. &Varon, S. (1990) Nerve growth factor infusion into the denervated adult rat hippocampal formation promotes its cholinergic reinnervation.Journal of Neuroscience 10, 3087–92.

    Google Scholar 

  • Hagg, T., Gulati, A. K., Behzadian, M. A., Vahesing, H. L., Varon, S. &Manthorpe, M. (1991) Nerve growth factor promotes CNS cholinergic axonal regeneration into acellular peripheral nerve grafts.Experimental Neurology 112, 79–88.

    Google Scholar 

  • Hall, S. &Berry, M. (1989) Electron microscopic study of the interaction of axons and glia at the site of anastomosis between the optic nerve and cellular sciatic nerve grafts.Journal of Neurocytology 18, 171–84.

    Google Scholar 

  • Henrikson, C. K. &Vaughn, J. E. (1974) Fine structural relationships between neurites and radial glial processes in developing mouse spinal cord.Journal of Neurocytology 3, 659–75.

    Google Scholar 

  • Heumann, R., Korsching, S., Bandtlow, C. &Thoenen, H. (1987) Changes of nerve growth factor synthesis in nonneuronal cells in response to sciatic nerve transection.Journal of Cell Biology 104, 1623–31.

    Google Scholar 

  • Hisanaga, K. &Sharp, F. R. (1990) Diffisible neurotrophic factors for thalamic neurons are released from target neocortex and non-target cerebellum.Progress in Brain Research 82, 67–71.

    Google Scholar 

  • Jessen, K. R., Mirsky, R. &Morgan, L. (1987) Axonal signals regulate the differentiation of non-myelin-forming Schwann cells: an immunohistochemical study of galactocerebroside in transected and regenerating nerves.Journal of Neuroscience 7, 3362–9.

    Google Scholar 

  • Karlsson, U. (1967) Observations on the postnatal development of neuronal structures in the lateral geniculate nucleus of the rat by electron microscopy.Journal of Ultrastructure Research 17, 158–75.

    Google Scholar 

  • Keirstead, S. A., Vidal-Sanz, M., Rasminsky, M., Aguayo, A. J., Levesque, M. &So, K-F. (1985) Responses to light of retinal neurons regenerating axons into peripheral nerve grafts in the rat.Brain Research 359, 402–6.

    Google Scholar 

  • Keirstead, S. A., Rasminsky, M., Fukuda, Y., Carter, D. A., Aguayo, A. J. &Vidal-Sanz, M. (1989) Electrophysiologic responses in hamster superior colliculus evoked by regenerating retinal axons.Science 246, 255–7.

    Google Scholar 

  • Kuhlengel, K. R., Bunge, M. B., Bunge, R. P. &Burton, H. (1990) Implantation of cultured sensory neurons and Schwann cells into lesioned neonatal rat spinal cord. II. Implant characteristics and examination of corticospinal tract growth.Journal of Comparative Neurology 293, 74–91.

    Google Scholar 

  • Lieberman, A. R. &Webster, K. E. (1974) Aspects of the synaptic organization of intrinsic neurons in the dorsal lateral geniculate nucleus. An ultrastructural study of the normal and of the experimentally deafferented nucleus in the rat.Journal of Neurocytology 3, 677–710.

    Google Scholar 

  • Lund, R. D. &Cunningham, T. J. (1972) Aspects of synaptic and laminar organization of the mammalian lateral geniculate body.Investigative Ophthalmology 11, 291–302.

    Google Scholar 

  • Maisonpierre, P. C., Belluscio, L., Friedman, B., Alderson, R. F., Wiegand, S. J., Furth, M. E., Lindsay, R. M. &Yancopoulos, G. D. (1990) NT-3, BDNF, and NGF in the developing rat nervous system: parallel as well as reciprocal patterns of expression.Neuron 5, 501–9.

    Google Scholar 

  • Mesulam, M-M. (1978) Tetramethyl benzidine for horseradish peroxidase neurohistochemistry: a non-carcinogenic blue reaction-product with superior sensitivity for visualizing neural afferents and efferents.Journal of Histochemistry and Cytochemistry 26, 106–17.

    Google Scholar 

  • Mori, S. &Leblond, C. P. (1970) Electron microscopic identification of three classes of oligodendrocytes and a preliminary study of their proliferative activity in the corpus callosum of young rats.Journal of Comparative Neurology 139, 1–30.

    Google Scholar 

  • Morrow, D. R., Campbell, G., Anderson, P. N. &Lieberman, A. R. (1991) Factors affecting regenerative axonal growth of adult CNS neurons into peripheral nerve grafts: studies using retrograde cell labelling with HRP.Journal of Anatomy 176, 229–30.

    Google Scholar 

  • Morrow, D. R., Campbell, G., Lieberman, A. R. &Anderson, P. N. (1993) Differential regenerative growth of CNS axons into tibial and peroneal nerve grafts in the thalamus of adult rats.Experimental Neurology, in press.

  • Munz, M., Rasminsky, M., Aguayo, A. J., Vidal-Sanz, M. &Devor, M. (1985) Functional activity of brainstem neurons regenerating axons along peripheral nerve grafts.Brain Research 340, 115–25.

    Google Scholar 

  • Paino, C. L. &Bunge, M. B. (1991) Induction of axon growth into Schwann cell implants grafted into lesioned adult rat spinal cord.Experimental Neurology 114, 254–7.

    Google Scholar 

  • Parnavelas, J. G., Luder, R., Pollard, S. G., Sullivan, K. &Lieberman, A. R. (1983) A qualitative and quantitative ultrastructural study of glial cells in the developing visual cortex of the rat.Philosophical Transactions of the Royal Society of London B301, 55–84.

    Google Scholar 

  • Pellegrino, L. J., Pellegrino, A. S. &Cushman, A. J. (1979)A Stereotaxic Atlas of the Rat Brain. 2nd ed. New York: Plenum Press.

    Google Scholar 

  • Peters, A., Palay, S. L. &Webster, H. De F. (1991)The fine structure of the nervous system. 3rd ed. Oxford and New York: Oxford University Press.

    Google Scholar 

  • Reier, P. J., Stensaas, L. J. &Guth, L. (1983) The astrocyte scar as an impediment to regeneration in the central nervous system. InSpinal Cord Reconstruction (edited byKao, C. C., Bunge, R. P. &Reier, P. J.), pp. 163–95. New York: Raven Press.

    Google Scholar 

  • Richardson, P. M., McGuinness, U. M. &Aguayo, A. J. (1980) Axons from CNS neurones regenerate into PNS grafts.Nature 284, 264–5.

    Google Scholar 

  • Richardson, P. M., McGuinness, U. M. &Aguayo, A. J. (1982) Peripheral nerve autografts to the rat spinal cord: studies with axonal tracing methods.Brain Research 237, 147–62.

    Google Scholar 

  • Richardson, P. M., Issa, V. M. K. &Aguayo, A. J. (1984) Regeneration of long spinal axons in the rat.Journal of Neurocytology 13, 165–82.

    Google Scholar 

  • Sendtner, M., Stöckli, K. A. &Thoenen, H. (1992) Synthesis and localization of ciliary neurotrophic factor in the sciatic nerve of the adult rat after lesion and during regeneration.Journal of Cell Biology 118, 139–48.

    Google Scholar 

  • Sharp, F. R. &Gonzalez, M. F. (1986) Fetal cortical transplants ameliorate thalamic atrophy ipsilateral to neonatal frontal cortex lesions.Neuroscience Letters 71, 247–51.

    Google Scholar 

  • Skene, J. H. P. (1984) Growth-associated proteins and the curious dichotomies of nerve regeneration.Cell 37, 697–700.

    Google Scholar 

  • Skene, J. H. P. (1989) Axonal growth-associated proteins.Annual Review of Neuroscience 12, 127–56.

    Google Scholar 

  • Skene, J. H. P. &Willard, M. (1981a) Changes in axonally transported proteins during axon regeneration in toad retinal ganglion cells.Journal of Cell Biology 89, 86–95.

    Google Scholar 

  • Skene, J. H. P. &Willard, M. (1981b) Axonally transported proteins associated with axon growth in rabbit central and peripheral nervous system.Journal of Cell Biology 89, 96–103.

    Google Scholar 

  • Smith, G. V. &Stevenson, J. A. (1988) Peripheral nerve grafts lacking viable Schwann cells fail to support central nervous system regeneration.Experimental Brain Research 69, 299–306.

    Google Scholar 

  • So, K -F, &Aguayo, A. J. (1985) Lengthy regrowth of cut axons from ganglion cells after peripheral nerve transplantation into the retina of adult rats.Brain Research 328, 349–54.

    Google Scholar 

  • So, K -F., Campbell, G. &Lieberman, A. R. (1985) Synaptic organization of the dorsal lateral geniculate nucleus in the adult hamster.Anatomy and Embryology 171, 223–34.

    Google Scholar 

  • Špaček, J. &Lieberman, A. R. (1974) Ultrastructure and three-dimensional organization of synaptic glomeruli in rat somatosensory thalamus.Journal of Anatomy 117, 487–516.

    Google Scholar 

  • Stensaas, L. J., Partlow, L. M., Burgess, P. R. &Horch, K. W. (1987) Inhibition of regeneration: the ultrastructure of reactive astrocytes and abortive axon terminals in the transition zone of the dorsal root.Progress in Brain Research 71, 457–68.

    Google Scholar 

  • Taylor, A. M., Anderson, P. N., Turmaine, M. &Lieberman, A. R. (1989) Early regenerative growth of retinal axons following optic tract section in neonatal hamsters.Neuroscience Letters Supplement 36, S68.

    Google Scholar 

  • Tetzlaff, W., Zwiers, H., Lederis, K., Cassar, L. &Bisby, M. A. (1989) Axonal transport and localization of B-50/GAP-43-like immunoreactivity in regenerating sciatic and facial nerves of the rat.Journal of Neuroscience 9, 1303–13.

    Google Scholar 

  • Vaudano, E., Campbell, G., Anderson, P. N., Davies, A. P., Schreyer, D. J. &Lieberman, A. R. (1992a) GAP-43 in adult rat thalamus following stab wounds or the implantation of living or dead nerve autografts.Neuroscience Letters Supplement 42, S18.

    Google Scholar 

  • Vaudano, E., Davies, A. P., Campbell, G., Davies, S. W., Anderson, P. N. &Lieberman, A. R. (1992b) NGF-receptor immunoreactivity in the thalamus of adult rats after stab wound lesion and in the presence of a tibial nerve autograft.European Journal of Neuroscience, in press.

  • Verhaagen, J., Oestreicher, A. B., Edwards, P. M., Veldman, H., Jennekens, F. G. I. &Gispen, W. H. (1989) Ultrastructural immunocytochemical localization of B-50/GAP-43, a protein kinase C substrate, in isolated nerve terminals and neuronal growth cones.Journal of Neurocytology 18, 479–89.

    Google Scholar 

  • Vidal-Sanz, M., Bray, G. M., Villegas-Perez, M. P., Thanos, S. &Aguayo, A. J. (1987) Axonal regeneration and synapse formation in the superior colliculus by retinal ganglion cells in the adult rat.Journal of Neuroscience 7, 2894–909.

    Google Scholar 

  • Vidal-Sanz, M., Bray, G. M. &Aguayo, A. J. (1991) Regenerated synapses persist in the superior colliculus after the regrowth of retinal ganglion cell axons.Journal of Neurocytology 20, 940–52.

    Google Scholar 

  • Vitkovic, L., Steisslinger, H. W., Aloyo, V. J. &Mesel, M. (1988) The 43-kDa neuronal growth associated protein (GAP-43) is present in plasma membranes of rat astrocytes.Proceedings of the National Academy of Sciences (USA) 85, 8296–300.

    Google Scholar 

  • Webster, H. De F. &Favilla, J. T. (1984) Development of peripheral nerve fibres. InPeripheral Neuropathy Vol. 1 (edited byDyck, P. J., Thomas, P. K., Lambert, E. H. &Bunge, R.), 329–59. Philadelphia: W. B. Sanders Co.

    Google Scholar 

  • Weinberg, E. L. &Raine, C. S. (1980) Reinnervation of peripheral nerve segments implanted into the rat central nervous system.Brain Research 198, 1–11.

    Google Scholar 

  • Weinberg, H. J. &Spencer, P. S. (1976) Studies on the control of myelinogenesis. II. Evidence for neuronal regulation of myelin production.Brain Research 113, 363–78.

    Google Scholar 

  • Weinberg, H. J. &Spencer, P. S. (1978) The fate of Schwann cells isolated from axonal contact.Journal of Neurocytology 7, 555–69.

    Google Scholar 

  • Williams, L. R., Manthorpe, M., Barbin, G., Nietosampedro, M., Cotman, C. W. &Varon, S. (1984) High ciliary neuronotrophic specific activity in rat peripheral nerve.International Journal of Developmental Neuroscience 2, 177–80.

    Google Scholar 

  • Wood, S. J., Pritchard, J. &Sofroniew, M. V. (1990) Re-expression of nerve growth factor receptor after axonal injury recapitulates a developmental event in motor neurons: differential regulation when regeneration is allowed or prevented.European Journal of Neuroscience 2, 650–7.

    Google Scholar 

  • Woolf, C. J., Reynolds, M. L., Molander, C., O'Brien, C., Lindsay, R. M. &Benowitz, L. I. (1990) The growth associated protein GAP-43 appears in dorsal root ganglion cells and in the dorsal horn of the rat spinal cord following peripheral nerve injury.Neuroscience 34, 465–78.

    Google Scholar 

  • Zhou, C-F., Lawrence, J. M., Morris, R. J. &Raisman, G. (1986) Migration of host astrocytes into superior cervical sympathetic ganglia autografted into the septal nuclei or choroid fissure of adult rats.Neuroscience 17, 815–27.

    Google Scholar 

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  1. Department of Anatomy and Developmental Biology, University College London, Gower Street, WC1E 6BT, London, UK

    G. Campbell, A. R. Lieberman, P. N. Anderson & M. Turmaine

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Campbell, G., Lieberman, A.R., Anderson, P.N. et al. Regeneration of adult rat CNS axons into peripheral nerve autografts: ultrastructural studies of the early stages of axonal sprouting and regenerative axonal growth. J Neurocytol 21, 755–787 (1992). https://doi.org/10.1007/BF01237903

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