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Profile of adult rat sensory neuron loss, apoptosis and replacement after sciatic nerve crush

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Journal of Neurocytology

Abstract

Following permanent transection of the adult rat sciatic nerve, sensory neuron apoptosis in the contributing L4 and L5 dorsal root ganglia can be observed for at least 6 months afterwards. To establish the profile of any sensory neuron apoptosis and loss over time when axonal regeneration is allowed, serial sections of L4 and L5 ganglia were examined and the neurons counted using a stereological technique 1, 2 and 3 months after crushing the right sciatic nerve at mid-thigh level. Our results show that an identical degree of sensory neuron loss and apoptosis occurs 1 month after crush as at 1 month after permanent transection. However, at 3 months no neurons undergoing apoptosis could be observed and no significant loss could be detected in the ipsilateral ganglia when compared to unoperated controls. One explanation was a neuronal replacement mechanism, which was investigated by administering bromodeoxyuridine to rats for 1 month after sciatic nerve transection or crush, prior to detection using immunohistochemistry on sections of their ganglia after 2 months. The presence of bromodeoxyuridine in the nuclei of occasional cells that would be counted as neurons on the basis of size and morphology indicates that a process of apparent neurogenesis may underlie the profile of sensory neuron loss after axotomy.

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References

  • ARVIDSSON, J., YGGE, J. & GRANT, G. (1986) Cell loss in lumbar dorsal root ganglia and transganglionic degeneration after sciatic nerve resection in the rat. Brain Research 373, 15–21.

    Google Scholar 

  • BARANOWSKI, A. P., PRIESTLEY, J. V. & MCMAHON, S. (1993) Substance P in cutaneous primary sensory neurons—A comparison of models of nerve injury that allow varying degrees of regeneration. Neuroscience 55, 1025–1036.

    Google Scholar 

  • BESTER, H., ALLCHORNE, A. J. & WOOLF, C. J. (1998) Recovery of C-fiber-induced extravasation following peripheral nerve injury in the rat. Experimental Neurology 154, 628–636.

    Google Scholar 

  • BRAZELTON, T. R., ROSSI, F. M. V., KESHET, G. I. & BLAU, H. M. (2000) From marrow to brain: Expression of neuronal phenotypes in adult mice. Science 290, 1775–1779.

    Google Scholar 

  • BRIDGE, P. M., BALL, D. J., MACKINNON, S. E., NAKAO, Y., BRANDT, K., HUNTER, D. A. & HERTL, C. (1994) Nerve crush injuries-a model for axonotmesis. Experimental Neurology 127, 284–290.

    Google Scholar 

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

    Google Scholar 

  • CIARONI, S., CECCHINI, T., CUPPINI, R., FERRI, P., AMBROGINI, P., BRUNO, C. & DEL GRANDE, P. (2000) Are there proliferating neuronal precursors in adult rat dorsal root ganglia? Neuroscience Letters 281, 69–71.

    Google Scholar 

  • CLARKE, P. G. H. (1999) Apoptosis versus necrosis: How valid a dichotomy for neurons? In Cell Death and Diseases of the Nervous System (edited by KOLIATSOS, V. E. & RATAN, R. R.) pp. 3–28. Totowa, NJ: Humana Press.

    Google Scholar 

  • COGGESHALL, R. E. (1992) A consideration of neural counting methods. Trends in Neurosciences 15, 9–13.

    Google Scholar 

  • COGGESHALL, R. E., LEKAN, H. A., DOUBELL, T. P., ALLCHORNE, A. & WOOLF, C. J. (1997) Central changes in primary afferent fibers following peripheral nerve lesions. Neuroscience 77, 1115–1122.

    Google Scholar 

  • CONOVER, W. J. (1980) Practical Nonparametric Statistics, 2nd edition, p. 231. New York/Chichester/Brisbane/ Toronto/Singapore: Wiley.

    Google Scholar 

  • COOPER-KUHN, C. M. & KUHN, H. G. (2002) Is it all DNA repair? Methodological considerations for detecting neurogenesis in the adult brain. Developmental Brain Research 134, 13–21.

    Google Scholar 

  • CORTI, S., LOCATELLI, F., DONADONI, C., STRAZZER, S., SALANI, S., DEL BO, R., CACCIALANZA, M., BRESOLIN, N., SCARLATO, G. & COMI, G. P. (2002) Neuroectodermal and microglial differentiation of bone marrowcells in the mouse spinal cord and sensory ganglia. Journal of Neuroscience Research 70, 721–733.

    Google Scholar 

  • DEGN, J., TANDRUP, T. & JAKOBSEN, J. (1999) Effect of nerve crush on perikaryal number and volume of neurons in adult rat dorsal root ganglion. Journal of Comparative Neurology 412, 186–192.

    Google Scholar 

  • DEVOR, M. & GOVRIN-LIPPMANN, R. (1985) Neurogenesis in adult rat dorsal root ganglia. Neuroscience Letters 61, 189–194.

    Google Scholar 

  • DEVOR, M., GOVRIN-LIPPMANN, R., FRANK, H. & RABER, P. (1985) Proliferation of primary sensory neurons in adult dorsal root ganglion and the kinetics of retrograde cell loss after sciatic nerve section. Somatosensory Research 3, 139–167.

    Google Scholar 

  • EDWARDS, S. N. & TOLKOVSKY, A. M. (1994) Characterization of apoptosis in cultured rat sympathetic neurons after nerve growth factor withdrawal. Journal of Cell Biology 124, 537–546.

    Google Scholar 

  • EKSTRÖM, P. A. R. (1995) Neurones and glial cells of the mouse sciatic nerve undergo apoptosis after injury in vivo and in vitro. Neuroreport 6, 1029–1033.

    Google Scholar 

  • FAWCETT, J. W. & KEYNES, R. J. (1990) Peripheral nerve regeneration. Annual Review of Neuroscience 13, 43–60.

    Google Scholar 

  • FRIEDE, R. L. & JOHNSTONE, M. A. (1967) Responses of thymidine labeling of nuclei in gray matter and nerve following sciatic transection. Acta Neuropathologica 7, 218–231.

    Google Scholar 

  • FUNAKOSHI, H., FRISEN, J., BARBANY, G., TIMMUSK, T., ZACHRISSON, O., VERGE, V. M. K. & PERSSON, H. (1993) Differential expression of mRNAs for neurotrophins and their receptors after axotomy of the sciatic nerve. Journal of Cell Biology 123, 455–465.

    Google Scholar 

  • GEUNA, S., BORRIONE, P. & FILOGAMO, G. (2002) Postnatal histogenesis in the peripheral nervous system. International Journal of Developmental Neuroscience 20, 475–479.

    Google Scholar 

  • GREENWOOD, A. L., TURNER, E. E. & ANDERSON, D. J. (1999) Identification of dividing, determined sensory neuron precursors in the mammalian neural crest. Development 126, 3545–3559.

    Google Scholar 

  • GROVES, M. J., CHRISTOPHERSON, T., GIOMETTO, B. & SCARAVILLI, F. (1997) Axotomy-induced apoptosis in adult rat primary sensory neurons. Journal of Neurocytology 26, 615–624.

    Google Scholar 

  • GROVES, M. J., AN, S.-F., GIOMETTO, B. & SCARAVILLI, F. (1999) Inhibition of sensory neuron apoptosis and prevention of loss by NT-3 administration following axotomy. Experimental Neurology 155, 284–294.

    Google Scholar 

  • GROVES, M. J., SCHÄNZER, A., AN, S.-F., SIMPSON, A. J. & SCARAVILLI, F. (2001) Effects of axonotmesis upon adult rat dorsal root ganglion neurons. Journal of the Peripheral Nervous System 6, 144.

    Google Scholar 

  • HAMMARBERG, H., PIEHL, F., CULLHEIM, S., FJELL, J., HOKFELT, T. & FRIED, K. (1996) GDNF mRNA in Schwann cells andDRGsatellite cells after chronic sciatic nerve injury. Neuroreport 7, 857–860.

    Google Scholar 

  • HIMES, B. T. & TESSLER, A. (1989) Death of some dorsal root ganglion neurons and plasticity of others following sciatic nerve section in adult and neonatal rats. Journal of Comparative Neurology 284, 215–230.

    Google Scholar 

  • HU, P. & MCLACHLAN, E. M. (2000) Distinct sprouting responses of sympathetic and peptidergic sensory axons proximal to a sciatic nerve transection in guinea pigs and rats. Neuroscience Letters 295, 59–63.

    Google Scholar 

  • JECKER, P., BEULEKE, A., DRESSENDÖRFER, I., PABST, R. & WESTERMANN, J. (1997) Long-term oral application of 5-bromo-2-deoxyuridine does not reliably label proliferating immune cells in the LEW rat. Journal of Histochemistry and Cytochemistry 45, 393–401.

    Google Scholar 

  • KRUGER, G. M., MOSHER, J. T., BIXBY, S., JOSEPH, N., IWASHITA, T. & MORRISON S. J. (2002) Neural crest stem cells persist in the adult gut but undergo changes in self-renewal, neuronal subtype potential, and factor responsiveness. Neuron 35, 657–669.

    Google Scholar 

  • LJUNGBERG, C., NOVIKOV, L., KELLERTH, J. O., EBENDAL, T. & WIBERG, M. (1999) The neurotrophins NGF and NT-3 reduce sensory neuronal loss in adult rat after peripheral nerve lesion. Neuroscience Letters 262, 29–32.

    Google Scholar 

  • LU, X. & RICHARDSON, P. M. (1991) Inflammation near the nerve cell body enhances axonal regeneration. Journal of Neuroscience 11, 972–978.

    Google Scholar 

  • MCKAY HART, A., BRANNSTROM, T., WIBERG, M. & TERENGHI, G. (2002) Primary sensory neurons and satellite cells after peripheral axotomy in the adult rat. Experimental Brain Research 142, 308–318.

    Google Scholar 

  • MITCHELL, D., IBRAHIM, S. & GUTERSON, B. A. (1985) Improved immunohistochemical localization of tissue antigens using modified methacarn fixation. Journal of Histochemistry and Cytochemistry 33, 491–495.

    Google Scholar 

  • NAMAKA, M. P., SAWCHUK, M., MACDONALD, S. C., JORDAN, L. M. & HOCHMAN, S. (2001) Neurogenesis in postnatal mouse dorsal root ganglia. Experimental Neurology 172, 60–69.

    Google Scholar 

  • POPKEN, G. J. & FAREL, P. B. (1997) Sensory neuron number in neonatal and adult rats estimated by means of stereologic and profile-based methods. Journal of Comparative Neurology 386,8–15.

    Google Scholar 

  • RAKIC, P. (2002) Adult neurogenesis in mammals: An identity crisis. Journal of Neuroscience 22, 614–618.

    Google Scholar 

  • RANSON, S. W. (1909) Alterations in the spinal ganglion cells following neurotomy. Journal of Comparative Neurology and Psychology 19, 125–149.

    Google Scholar 

  • RICH, K. M., DISCH, S. P. & EICHLER, M. E. (1989) The influence of regeneration and nerve growth factor on the neuronal cell body reaction to injury. Journal of Neurocytology 18, 569–576.

    Google Scholar 

  • SCHMALBRUCH, H. (1987) Loss of sensory neurons after sciatic nerve section in the rat. The Anatomical Record 219, 323–329.

    Google Scholar 

  • SEBERT, M. E. & SHOOTER, E. M. (1993) Expression of mRNA for neurotrophic factors and their receptors in. the rat dorsal root ganglion and sciatic nerve following nerve injury. Journal of Neuroscience Research 36, 357–367.

    Google Scholar 

  • SINGH, R. P. & ZHOU, F. C. (2002) Progenitorship of the embryonic and adult dorsal root ganglia cells. Experimental Neurology 175, 433.

    Google Scholar 

  • STERIO, D. C. (1984) The unbiased estimation of number and sizes of arbitrary particles using the disector. Journal of Microscopy 134, 127–136.

    Google Scholar 

  • SWETT, J. E., HONG, C.-Z. & MILLER, P. G. (1995) Most dorsal root ganglion neurons of the adult rat survive nerve crush injury. Somatosensory and Motor Research 12, 177–189.

    Google Scholar 

  • TANDRUP, T. (1993) A method for unbiased and efficient estimation of number and mean volume of specified neuron subtypes in rat dorsal root ganglion. Journal of Comparative Neurology 329, 269–276.

    Google Scholar 

  • TANDRUP, T. (1995) Are the neurons in the dorsal root ganglion pseudounipolar? A comparison of the number of neurons and number of myelinated and unmyelinated fibres in the dorsal root. Journal of Comparative Neurology 357, 341–347.

    Google Scholar 

  • TANDRUP, T., WOOLF, C. J.& COGGESHALL, R. E. (2000) Delayed loss of small dorsal root ganglion cells after transection of the rat sciatic nerve. Journal of Comparative Neurology 422, 172–180.

    Google Scholar 

  • WOODBURY, D., SCHWARZ, E. J., PROCKOP, D. J. & BLACK, I. B. (2000) Adult rat and human bone marrow stromal cells differentiate into neurons. Journal of Neuroscience Research 61, 364–370.

    Google Scholar 

  • YGGE, J. (1989) Neuronal loss in lumbar dorsal root ganglia after proximal compared to distal sciatic nerve resection: A quantitative study in the rat. Brain Research 478, 193–195.

    Google Scholar 

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Authors and Affiliations

  1. Department of Molecular Pathogenesis, Institute of Neurology, University College London, Queen Square, London, WC1N 3BG

    M. J. Groves, A. Schänzer, A. J. Simpson, S.-F. An, L. T. Kuo & F. Scaravilli

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  1. M. J. Groves
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  2. A. Schänzer
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  3. A. J. Simpson
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  4. S.-F. An
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  5. L. T. Kuo
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  6. F. Scaravilli
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Groves, M.J., Schänzer, A., Simpson, A.J. et al. Profile of adult rat sensory neuron loss, apoptosis and replacement after sciatic nerve crush. J Neurocytol 32, 113–122 (2003). https://doi.org/10.1023/B:NEUR.0000005596.88385.ec

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  • DOI: https://doi.org/10.1023/B:NEUR.0000005596.88385.ec

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