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The induction of a regenerative propensity in sensory neurons following peripheral axonal injury

  • Published:
Journal of Neurocytology

Summary

Injury of the peripheral axons of primary sensory neurons has been previously shown to increase the probability that the corresponding central axons would grow from the injured spinal cord into a peripheral nerve graft. This phenomenon has been used to investigate the nature of extrinsic cues from injured nerves that trigger an enhanced regenerative propensity within sensory neurons. In 13 groups of rats, a segment of the right sciatic nerve was grafted to the dorsal columns of the spinal cord and the left sciatic nerve was subjected to mechanical injury, injection of colchicine or infusion of nerve growth factor. Subsequently, neurons in lumbar dorsal root ganglia with axons growing from the spinal cord into a graft were identified by retrograde perikaryal labelling and compared for the two sides. The aim was to mimic or modify the inductive effect of nerve transaction by alternative or additional manipulation of the nerve. Growth of central axons was less enhanced by peripheral axonal interruption if the length of the proximal stump was increased or if a distal stump was present to permit rapid regeneration. However, the regenerative response following nerve transection was altered little by crushing the proximal stump or injecting it with colchicine or nerve growth factor. It is suggested that sensory neurons are stimulated to regenerate by peripheral axonal injuries that reduce some normal retrograde regulatory influence of Schwann cells.

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References

  • Abercrombie, M. &Johnson, M. L. (1946) Quantitative histology of Wallerian degeneration. I. Nuclear population in rabbit sciatic nerve.Journal of Anatomy 80, 37–50.

    Google Scholar 

  • Aldskogius, H., Arvidsson, J. &Grant, G. (1985) The reaction of primary sensory neurons to peripheral nerve injury with particular emphasis on transganglionic changes.Brain Research Reviews 10, 27–46.

    Google Scholar 

  • Aldskogius, H. &Risling, M. (1983) Preferential loss of unmyelinated L7 dorsal root axons following sciatic nerve resection in kittens.Brain Research 289, 358–61.

    Google Scholar 

  • Aletta, J. M. &Goldberg, D. J. (1984) Routing of transmitter and other changes in fast axonal transport after transection of one branch of the bifurcate axon of an identified neuron.Journal of Neuroscience 4, 1800–8.

    Google Scholar 

  • Anderson, H. K. (1902) The nature of the lesions which hinder the development of nerve-cells and their processes.Journal of Physiology 28, 499–513.

    Google Scholar 

  • Arvidsson, J. &Aldskogius, H. (1982) Effect of repeated hypoglossal nerve lesions on the number of neurons in the hypoglossal nucleus of adult rats.Experimental Neurology 75, 520–4.

    Google Scholar 

  • Earth, E.-M., Korshing, S. &Thoenen, H. (1984) Regulation of nerve growth factor synthesis and release in organ cultures of rat iris.Journal of Cell Biology 99, 839–43.

    Google Scholar 

  • Bisby, M. A. &Bulger, V. T. (1977) Reversal of axonal transport at a nerve crush.Journal of Neurochemistry 29, 313–20.

    Google Scholar 

  • Bisby, M. A. &Keen, P. (1985) The effect of a conditioning lesion on the regeneration rate of peripheral nerve axons containing substance P.Brain Research 336, 201–6.

    Google Scholar 

  • Brown, A. G. (1968) Cutaneous afferent fibre collaterals in the dorsal columns of the cat.Experimental Brain Research 5, 293–305.

    Google Scholar 

  • Cangiano, A. &Fried, J. A. (1977) The production of denervation-like changes in rat muscle by colchicine, without interference with axonal transport or muscle activity.Journal of Physiology 265, 63–84.

    Google Scholar 

  • Cavanaugh, M. W. (1951) Quantitative effects of the peripheral innervation area on nerves and spinal ganglion cells.Journal of Comparative Neurology 94, 181–219.

    Google Scholar 

  • Chapman, C. A., Banks, B. E. C., Vernon, C. A. &Walker, J. M. (1981) The isolation and characterisation of nerve growth factor from the prostate gland of the guinea-pig.European Journal of Biochemistry 115, 347–51.

    Google Scholar 

  • Collins, F. (1985) Electrophoretic similarity of the ciliary ganglion survival factors from different tissues and species.Developmental Biology 109, 255–8.

    Google Scholar 

  • Cragg, B. G. (1970) What is the signal for chromatolysis?Brain Research 23, 1–21.

    Google Scholar 

  • Csillik, B., Schwab, M. E. &Thoenen, H. (1985) Transganglionic regulation of central terminals of dorsal root ganglion cells by nerve growth factor (NGF).Brain Research 331, 11–15.

    Google Scholar 

  • Ebendal, T., Jordell-Kylberg, A. &Söderström, S. (1978) Stimulation by tissue explants on nerve fibre outgrowth in culture. InFormshaping Movements in Neurogenesis (edited byJacobson, C.-O. &Ebendal, T.), pp. 235–43. Stockholm: Almqvist and Wiksel.

    Google Scholar 

  • Fitzgerald, M., Wall, P. D., Goedert, M. &Emson, P. C. (1985) Nerve growth factor counteracts the neurophysiological and neurochemical effects of chronic sciatic nerve section.Brain Research 332, 131–41.

    Google Scholar 

  • Fitzgerald, M., Woolf, C. J., Gibson, S. J. &Mallaburn, P. S. (1984) Alterations in the structure, function, and chemistry of C fibers following local application of vinblastine to the sciatic nerve of the rat.Journal of Neuroscience 4, 430–41.

    Google Scholar 

  • Forman, D. S., Wood, D. K. &Desilva, S. (1979) Rate of regeneration of sensory axons in transected rat sciatic nerve repaired with epineurial sutures.Journal of the Neurological Sciences 44, 55–9.

    Google Scholar 

  • Goedert, M., Stoeckel, K. &Otten, U. (1981) Biological importance of the retrograde transport of nerve growth factor in sensory neurons.Proceedings of the National Academy of Sciences USA 78, 5895–8.

    Google Scholar 

  • Gordon, T., Hoffer, J. A., Jhamandas, J. &Stein, R. B. (1980) Long-term effects of axotomy on neural activity during cat locomotion.Journal of Physiology 303, 243–63.

    Google Scholar 

  • Grafstein, B. &McQuarrie, I. G. (1978) The role of the nerve cell body in axonal regeneration. InNeuronal Plasticity (edited byCotman, C. W.), pp. 155–95. New York: Raven Press.

    Google Scholar 

  • Hanson, M. &Edström, A. (1978) Mitosis inhibitors and axonal transport.International Review of Cytology, Suppl.7, 373–402.

    Google Scholar 

  • Hare, W. K. &Hinsey, J. C. (1940) Reactions of dorsal root ganglion cells to section of peripheral and central processes.Journal of Comparative Neurology 73, 489–502.

    Google Scholar 

  • Horch, K. W., Burgess, P. R. &Whitehorn, D. (1976) Ascending collaterals of cutaneous neurons in the fasciculus gracilis of the cat.Brain Research 117, 1–17.

    Google Scholar 

  • Hulsebosch, C. E., Coggeshall, R. E. &Perez-Polo, J. R. (1984) Increased numbers of thoracic dorsal root axons in rats given antibodies to nerve growth factor.Science 225, 525–6.

    Google Scholar 

  • Konigsmark, B. W. (1970) Methods for the counting of neurons. InContemporary Research Methods in Neuroanatomy (edited byNauta, W. J. H. &Ebbeson, S. O. E.), pp. 315–40. New York: Springer-Verlag.

    Google Scholar 

  • Korsching, S. &Thoenen, H. (1983) Quantitative demonstration of the retrograde axonal transport of endogenous nerve growth factor.Neuroscience Letters 39, 1–4.

    Google Scholar 

  • Korsching, S. &Thoenen, H. (1985) Treatment with 6-hydroxydopamine and colchicine decreases nerve growth factor levels in sympathetic ganglia and increases them in the corresponding target tissues.Journal of Neuroscience 5, 1058–61.

    Google Scholar 

  • Kristensson, K. &Olsson, Y. (1975) Retrograde transport of horseradish peroxidase in transected axons. II. Relations between rate of transfer from the site of injury to the perikaryon and onset of chromatolysis.Journal of Neurocytology 4, 653–61.

    Google Scholar 

  • Lieberman, A. R. (1974) Some factors affecting retrograde neuronal responses to axonal lesions. InEssays on the Nervous System (edited byBellairs, R. &Gray, E. G.), pp. 71–105. New York: Clarenden Press.

    Google Scholar 

  • Mata, M., Staple, J. &Fink, D. J. (1985) Ultrastructural localization of slow retrograde axonal transport: an autoradiographic study.Journal of Neuroscience 5, 2900–8.

    Google Scholar 

  • McQuarrie, I. G., Grafstein, B. &Gershon, M. D. (1977) Axonal regeneration in the rat sciatic nerve: effect of a conditioning lesion and of dbcAMP.Brain Research 132, 443–53.

    Google Scholar 

  • Mesulam, M.-M. (1978) Tetramethylbenzidine for horseradish peroxidase neurohistochemistry.Journal of Histochemistry and Cytochemistry 26, 106–17.

    Google Scholar 

  • Mobley, W. C., Schenker, A. &Shooter, E. M. (1976) Characterization and isolation of proteolytically modified nerve growth factor.Biochemistry 15, 5543–51.

    Google Scholar 

  • Perry, G. W., Krayanek, S. R. &Wilson, D. L. (1983) Protein synthesis and rapid axonal transport during regrowth of dorsal root axons.Journal of Neurochemistry 40, 1590–8.

    Google Scholar 

  • Pilar, G. &Landmesser, L. (1972) Axotomy mimicked by localized colchicine application.Science 177, 1116–8.

    Google Scholar 

  • Ranson, S. W. (1906) Retrograde degeneration in the spinal nerves.Journal of Comparative Neurology 16, 265–93.

    Google Scholar 

  • Rich, K. M., Yip, H. K., Osborne, P. A., Schmidt, R. E. &Johnson, E. M. (1984) Role of nerve growth factor in the adult dorsal root ganglion neuron and its response to injury.Journal of Comparative Neurology 230, 110–18.

    Google Scholar 

  • Richardson, P. M. &Ebendal, T. (1982) Nerve growth activities in rat peripheral nerve.Brain Research 246, 57–64.

    Google Scholar 

  • Richardson, P. M., Ebendal, T. &Riopelle, R. J. (1985) Nerve growth and nerve growth factor within peripheral nervous tissue. InNeural Grafting in the Mammalian CNS, Fernström Foundation Series, Vol. 5 (edited byBjörklund, A. &Stenevi, U.), pp. 319–27. Amsterdam: Elsevier.

    Google Scholar 

  • Richardson, P. M. &Issa, V. M. K. (1984) Peripheral injury enhances central regeneration of primary sensory neurones.Nature 309, 791–3.

    Google Scholar 

  • Richardson, P. M. &Riopelle, R. J. (1984) Uptake of nerve growth factor along peripheral and spinal axons of primary sensory neurons.Journal of Neuroscience 4, 1683–9.

    Google Scholar 

  • Richardson, P. M., Verge Issa, V. M. K. &Riopelle, R. J. (1986) Distribution of neuronal receptors for nerve growth factor in the rat.Journal of Neuroscience (in press).

  • Risling, M., Aldskogius, H., Hildebrand, C. &Remahl, S. (1983) Effects of sciatic nerve resection on L7 spinal roots and dorsal root ganglia in adult cats.Experimental Neurology 82, 568–80.

    Google Scholar 

  • Schwartz, J. P., Pearson, J. &Johnson, E. M. (1982) Effect of exposure to anti-NGF on sensory neurons of adult rats and guinea pigs.Brain Research 244, 378–81.

    Google Scholar 

  • Scott, S. A. &Muller, K. J. (1980) Synapse regeneration and signals for directed axonal growth in the central nervous system of the leech.Developmental Biology 80, 345–63.

    Google Scholar 

  • Singer, P. A., Mehler, S. &Fernandez, H. L. (1982) Blockade of retrograde axonal transport delays the onset of metabolic and morphologic changes induced by axotomy.Journal of Neuroscience 2, 1299–306.

    Google Scholar 

  • Stoeckel, K., Schwab, M. &Thoenen, H. (1975) Specificity of retrograde transport of nerve growth factor (NGF) in sensory neurons: a biochemical and morphological study.Brain Research 89, 1–14.

    Google Scholar 

  • Sutter, A., Riopelle, R. J., Harris-Warrick, R. M. &Shooter, E. M. (1979) Nerve growth factor receptors. Characterization of two distinct classes of binding sites on chick embryo sensory ganglia cells.Journal of Biological Chemistry 254, 5972–82.

    Google Scholar 

  • Tessler, A., Himes, B. T., Krieger, N. R., Murray, M. &Goldberger, M. E. (1985) Sciatic nerve transection produces death of dorsal root ganglion neurons and reversible loss of substance P in the spinal cord.Brain Research 332, 209–18.

    Google Scholar 

  • Watson, W. E. (1968) Observations on the nucleolar and total cell body nucleic acid of injured nerve cells.Journal of Physiology 196, 655–76.

    Google Scholar 

  • Whitsel, B. L., Petrucelli, L. M. &Sapiro, G. (1969) Modality representation in the lumbar and cervical fasciculus gracilis of squirrel monkeys.Brain Research 15, 67–78.

    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 

  • Wujek, J. R. &Lasek, R. J. (1983) Correlation of axonal regeneration and slow component B in two branches of a single axon.Journal of Neuroscience 3, 243–51.

    Google Scholar 

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  1. Division of Neurosurgery, McGill University and Montreal General Hospital, H3G 1A4, Montreal, Canada

    P. M. Richardson & V. M. K. Verge

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  1. P. M. Richardson
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  2. V. M. K. Verge
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Richardson, P.M., Verge, V.M.K. The induction of a regenerative propensity in sensory neurons following peripheral axonal injury. J Neurocytol 15, 585–594 (1986). https://doi.org/10.1007/BF01611859

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  • DOI: https://doi.org/10.1007/BF01611859

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