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Human dorsal root ganglion neurons from embryonic donors extend axons into the host rat spinal cord along laminin-rich peripheral surroundings of the dorsal root transitional zone

  • Published:
Journal of Neurocytology

Abstract

Following dorsal root crush, the lesioned axons regenerate in the peripheral compartment of the dorsal root, but stop at the boundary between the peripheral and the central nervous system, the dorsal root transitional zone. We have previously shown that fibres from human fetal dorsal root ganglia grafted to adult rat hosts are able to grow into the spinal cord, but were not able to specify the route taken by the ingrowing fibres. In this study we have challenged the dorsal root transitional zone astrocyte boundary with human dorsal root ganglion transplants from 5–8-week-old embryos. By tracing immunolabelled human fibres in serial sections, we found that fibres consistently grow around the dorsal root transitional zone astrocytes in laminin-rich peripheral surroundings, and extend into the host rat spinal cord along blood vessels, either into deep or superficial laminae of the dorsal horn, or into the dorsal funiculus. Human fibres that did not have access to blood vessels grew on the spinal cord surface. These findings indicate, that in spite of a substantial growth capacity by axons from human embryonic dorsal root ganglion cells as well as their tolerance to non-permissive factors in the mature mammalian CNS, these axons are still sensitive to the repellent effects of astrocytes of the mature dorsal root transitional zone. Furthermore, this axonal ingrowth is consistently associated with laminin-expressing structures until the axons reach the host spinal cord.

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References

  • Berthold, C.-H., Carlstedt, T. & Corneliusson, O. (1984) Anatomy of the nerve root at the central–peripheral transitional region. In Peripheral Neuropathy, Vol. 1, 2nd edn (edited by Dyck, P. J., Thomas, P. K., Lambert, E. H. & Bunge, R. P.) pp. 150–70. Philadelphia: W. B. Saunders.

    Google Scholar 

  • Bignami, A., Chi, N. H. & Dahl, D. (1984) Regenerating dorsal roots and the nerve entry zone: an immunofluorescence study with neurofilament and laminin antisera. Experimental Neurology 85, 426–35.

    Google Scholar 

  • BjÖrklund, A. & Lindvall, O. (1979) Regeneration of normal terminal innervation of the globus pallidus by collaterals from the nigro-striatal pathway. Brain Research 171, 271–93.

    Google Scholar 

  • Burden-Gulley, S. M., Payne, H. R. & Lemmon, V. (1995) Growth cones are actively influenced by substrate-bound adhesion molecules. Journal of Neuroscience 15, 4370–81.

    Google Scholar 

  • Cajal, S. R. y. (1928) Degeneration and Regeneration of the Nervous System. London: Oxford University Press.

    Google Scholar 

  • Carlstedt, T. (1983) Regrowth of anastomosed ventral root nerve fibers in the dorsal root of rats. Brain Research 272, 162–5.

    Google Scholar 

  • Carlstedt, T. (1985a) Regenerating axons form nerve terminals at astrocytes. Brain Research 347, 188–91.

    Google Scholar 

  • Carlstedt, T. (1985b) Regrowth of cholinergic and catecholaminergic neurons along a peripheral and central nervous pathway. Neuroscience 15, 507–18.

    Google Scholar 

  • Chong, M. S., Woolf, C. J., Turmaine, M., Emson, P. C. & Anderson, P. N. (1996) Intrinsic versus extrinsic factors in determining regeneration of the central processes of rat dorsal root ganglion neurons: the influences of a peripheral nerve graft. Journal of Comparative Neurology 370, 97–104.

    Google Scholar 

  • David, S., Braun, P. E., Jackson, D. L., Kottis, V. & McKerracher, L. (1995) Laminin overrides the inhibitory effects of peripheral nervous system and central nervous system myelin-derived inhibitors of neurite growth. Journal of Neuroscience Research 42, 594–602.

    Google Scholar 

  • Davies, S. J., Field, P. M. & Raisman, G. (1994) Long interfascicular axon growth from embryonic neurons transplanted into adult myelinated tracts. Journal of Neuroscience 14, 1596–612.

    Google Scholar 

  • England, M. A. (1990) A Colour Atlas of Life Before Birth. 2nd edn. Aylesbury, Bucks: Hazell Books.

    Google Scholar 

  • Fawcett, J. (1994) Astrocytes and axon regeneration in the central nervous system. Journal of Neurology 214, S25–8.

    Google Scholar 

  • Fawcett, J. W., Fersht, N., Housden, L., Schachner, M. & Pesheva, P. (1992) Axonal growth on astrocytes is not inhibited by oligodendrocytes. Journal of Cell Science 103, 571–9.

    Google Scholar 

  • Fok-Seang, J., Smith-Thomas, L.C., Meiners, S., Muir, E., Du, J. S., Housden, E., Johnson, A. R., Faissner, A., Geller, H. M., Keynes, R. J., Rogers, J. H. & Fawcett, J. W. (1995) An analysis of astrocytic cell lines with different abilities to promote axon growth. Brain Research 689, 207–23.

    Google Scholar 

  • Fraher, J. P. (1992) The CNS–PNS transitional zone of the rat. Morphometric studies at cranial and spinal levels. Progress in Neurobiology 38, 261–316.

    Google Scholar 

  • FrisÉn, J. Haegerstrand, A., Risling, M., Fried, K., Johnsson, C. B., Hammarberg, H., Elde, R., HÖkfelt, T. T. & Cullheim, S. (1995) Spinal axons in central nervous system scar tissue are closely related to laminin-immunoreactive astrocytes. Neuroscience 65, 293–304.

    Google Scholar 

  • Gillen, C., Korfhage, C. & MÜller, H. W. (1997) Gene expression in nerve regeneration. The Neuroscientist 3, 112–22.

    Google Scholar 

  • Golding, J. P., Shewan, D., Berry, M. & Cohen, J. (1996) An in vitro model of the rat dorsal root entry zone reveals developmental changes in the extent of sensory axon growth into the spinal cord. Molecular and Cellular Neuroscience 7, 191–203.

    Google Scholar 

  • Hagg, T., Muir, D., Engvall, E., Varon, S. & Manthorpe, M. (1989) Laminin-like antigen in rat CNS neurons: distribution and changes upon brain injury and nerve growth factor treatment. Neuron 3, 721–32.

    Google Scholar 

  • Hunter, D. D., Llinas, R., Ard, M., Merlie, J. P. & Sanes, J. R. (1992) Expression of s-laminin and laminin in the developing rat central nervous system. Journal of Comparative Neurology 323, 238–51.

    Google Scholar 

  • Kozlova, E. N., StrÖmberg, I., Bygdeman, M. & Aldskogius, H. (1995) Peripherally grafted human foetal dorsal root ganglion cells extend axons into the spinal cord of adult host rats by circumventing dorsal root entry zone astrocytes. NeuroReport 6, 269–72.

    Google Scholar 

  • Li, Y. & Raisman, G. (1993) Long axon growth from embryonic neurons transplanted into myelinated tracts of the adult rat spinal cord. Brain Research 629, 115–27.

    Google Scholar 

  • Li, Y. & Raisman, G. (1994) Schwann cells induce sprouting in motor and sensory axons in the adult rat spinal cord. Journal of Neuroscience 14, 4050–63.

    Google Scholar 

  • Liuzzi, F. J. & Lasek, R. J. (1987) Astrocytes block axonal regeneration in mammals by activating the physiological stop pathway. Science 237, 642–4.

    Google Scholar 

  • Pindzola, R. R., Doller, C. & Silver, J. (1993) Putative inhibitory extracellular matrix molecules at the dorsal root entry zone of the spinal cord during and after root and sciatic nerve lesions. Experimental Neurology 156, 34–48.

    Google Scholar 

  • Reier, P. J. & Houle, J. (1998) The glial scar: its bearing on axonal elongation and transplantation approaches to CNS repair. In Advances in Neurology, Vol. 47, Functional Recovery in Neurological Disease (edited by Waxman, S. G.) pp. 87–138.

  • 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. & Verge, V. M. (1986) The induction of a regenerative propensity in sensory neurons following peripheral axonal injury. Journal of Neurocytology 15, 585–94.

    Google Scholar 

  • Schnell, L. & Schwab, M. E. (1990) Axonal regeneration in the rat spinal cord produced by an antibody against myelin associated neurite growth inhibitors. Nature 343, 269–72.

    Google Scholar 

  • Schwab, M. E., Kapfhammer, J. P. & Bandtlow, C. E. (1993) Inhibitors of neurite growth. Annual Review of Neuroscience 16, 565–95.

    Google Scholar 

  • Smith-Thomas, C. L. Fok-Seang, J., Stevens, J., Du, J. S., Muir, E., Faissner, A., Geller, H. M., Rogers, J. H. & Fawcett, J. W. (1994) An inhibitor of neurite outgrowth produced by astrocytes. Journal of Cell Science 107, 1687–95.

    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 

  • Tomaselli, K. J., Doherty, P., Emmett, C. J., Damsky, C. H., Walsh, F. S. & Reichardt, L. F. (1993) Expression of b1 integrins in sensory neurons of the dorsal root ganglion and their function in neurite outgrowth on two laminin isoforms. Journal of Neuroscience 13, 4880–8.

    Google Scholar 

  • Wictorin, K., Lagenauer, C. F., Lund, R. D. & BjÖrklund, A. (1991) Efferent projections to the host brain from intrastriatal striatal mouse-to-rat grafts: time course and tissue-type specificity as revealed by a mouse specific neuronal marker. European Journal of Neuroscience 3, 86–101.

    Google Scholar 

  • Wictorin, K. & BjÖrklund, A. (1992) Axon outgrowth from grafts of human embryonic spinal cord in the lesioned adult rat spinal cord. NeuroReport 3, 1045–8.

    Google Scholar 

  • Wictorin, K., Brundin, P., Sauer, H., Lindvall, O. & BjÖrklund, A. (1992) Long distance axonal growth from human dopaminergic mesencephalic neuroblasts implanted along the nigrostriatal pathway in 6-hydroxydopamine lesioned adult rats. Journal of Comparative Neurology 323, 475–94.

    Google Scholar 

  • Wiklund, L. & BjÖrklund, A. (1980) Mechanisms of regrowth in the bulbospinal system following 5,6-dihydroxytryptamine induced axotomy. II. Fluorescence histochemical observations. Brain Research 191, 129–60.

    Google Scholar 

  • Xu, X. M., Chen, A., Guenard, V., Kleitman, N. & Bunge, M. B. (1997) Bridging Schwann cell transplants promote axonal regeneration from both the rostral and caudal stumps of transected adult rat spinal cord. Journal of Neurocytology 26, 1–16.

    Google Scholar 

  • Zhang, Y., Anderson, P. N., Campbell, G., Mohajeri, H., Schachner, M. & Lieberman, A. R. (1995) Tenascin-C expression by neurons and glial cells in the rat spinal cord: changes during postnatal development and after dorsal root or sciatic nerve injury. Journal of Neurocytology 24, 585–601.

    Google Scholar 

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Kozlova, E.N., Seiger, A. & Aldskogius, H. Human dorsal root ganglion neurons from embryonic donors extend axons into the host rat spinal cord along laminin-rich peripheral surroundings of the dorsal root transitional zone. J Neurocytol 26, 811–822 (1997). https://doi.org/10.1023/A:1018522616891

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