Summary
It is well known that the ends of normal axons can absorb exogenous tracer proteins, which are then transported intra-axonally to the neuronal perikarya. The object of this investigation was to determine whether the same phenomenon occurs in regenerating nerve fibres. Horseradish peroxidase (HRP) was applied to the hypoglossal nerves of rats immediately or at intervals of 12 h to 14 days after crushing. The enzyme was detected histochemically, 24 h later, in the neurones of the hypoglossal nucleus. The numbers of HRP-containing neurones declined abruptly after the 4th postoperative day. By this time most of the regenerating axons extended further distally in the nerve than the region permeated by the topically applied HRP, though some growth cones were still present near the site of injury even after 14 days. It is deduced that the growing tips of the regenerating axons, but not their more proximal parts, absorbed HRP for subsequent retrograde transport to their cell bodies.
In some of the rats a fluorescent tracer protein (thodamine B-labelled bovine serum albumin) was injected i.v. 1 h before death. Abnormal permeability of the endoneurial blood vessels was observed distal to the sites of crushing. The zone of increased permeability advanced distally at the same rate as that of the tips of the regenerating axons. It is suggested that the growth cones of regenerating axons may absorb proteins derived from the blood plasma. The retrograde axoplasmic transport of such substances to the cell bodies might be important in initiating and maintaining the neuronal metabolic changes necessary for the regeneration of severed axons.
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References
Arvidson, B.: Cellular uptake of exogenous horseradish peroxidase in mouse peripheral nerve. Acta Neuropathol. (Berl.)37, 35–41 (1977)
Bray, D.: Model for membrane movements in neural growth cone. Nature244, 93–95 (1973)
Broadwell, R. D., Brightman, M. W.: Entry of peroxidase into neurons of the central and peripheral nervous systems from extracerebral and cerebral blood. J. Comp. Neurol.166, 257–284 (1976)
Bunge, M. B.: Initial endocytosis of peroxidase or ferritin by growth cones of cultured nerve cells. J. Neurocytol.6, 407–439 (1977)
Cragg, B. G.: What is the signal for chromatolysis? Brain Res.23, 1–21 (1970)
De Vito, J. L., Clausing, K. W., Smith, O. B.: Uptake and transport of horseradish peroxidase by the cut end of the vagus nerve. Brain Res.82, 269–271 (1974)
Ebbot, S., Hendry, I.: Retrograde transport of nerve growth factor in the rat central nervous system. Brain Res.139, 160–163 (1978)
Furstman, L., Saporta, S., Kruger, L.: Retrograde axonal transport of horscradish peroxidase in sensory nerves and ganglion cells of the rat. Brain Res.84, 320–324 (1975)
Halperin, J. J., LaVail, J. H.: A study of the dynamics of retrograde transport and accumulation of HRP in injured neurons. Brain Res.100, 253–269 (1975)
Hedreen, J. C., McGrath, S.: Observations on labeling of neuronal cell bodies, axons and terminals after injection of horseradish peroxidase into the rat brain. J. Comp. Neurol.176, 225–246 (1977)
Heinicke, E. A., Kiernan, J. A.: Vascular permeability and axonal regeneration in skin autotransplanted into the brain. J. Anat.125, 409–420 (1978)
Hendry, I. A., Stockel, K., Thoenen, H., Iverson, L. L.: The retrograde axonal transport of nerve growth factor. Brain Res.68, 103–121 (1974)
Holmes, W.: Silver staining of nerve axons in paraffin sections. Anat. Rec.86, 157–187 (1943)
Holtzmann, E., Peterson, E. R.: Uptake of protein by mammalian neurons. J. Cell Biol.40, 863–868 (1969)
Kiernan, J. A.: An explanation of axonal regeneration in peripheral nerves and its failure in the central nervous system. Medical Hypotheses4, 15–26 (1978)
Klatzo, I., Miquel, J.: Observations on pinocytosis in nervous tissue. J. Neuropathol. Exp. Neurol.19, 475–487 (1960)
Kristensson, K.: Transport of fluorescent tracer proteins in peripheral nerves. Acta Neuropathol. (Berl.)16, 293–300 (1970)
Kristensson, K., Olsson, Y.: Retrograde axonal transport of protein. Brain Res.29, 363–365 (1971)
Kristensson, K., Olsson, Y.: Uptake and retrograde transport of protein tracers in hypoglossal neurons. Fate of the tracer and reaction of the nerve cell body. Acta Neuropathol. (Berl.)23, 43–47 (1973)
Kristensson, K., Olsson, Y.: Diffusion pathways and retrograde axonal transport of protein tracers in peripheral nerves. Prog. Neurobiol1, 85–109 (1973)
Kristensson, K., Olsson, Y.: Retrograde transport of horseradish peroxidase in transected axons. 1. Time relationships between transport and induction of chromatolysis. Brain Res.79, 101–109 (1974)
Kristensson, K., Olsson, Y.: Retrograde transport of horseradish peroxidase in transected axons. 2. Relations between rate of transfer from the injury to perikaryon and onset of chromatolysis. J. Neurocytol.4, 653–661 (1975)
Kristensson, K., Olsson, Y.: Retrograde transport of horseradish peroxidase in transected axons. 3. Entry into injured axons and subsequent localization in perikaryon. Brain Res.115, 201–213 (1976)
Kristensson, K., Olsson, Y., Sjöstrand, J.: Axonal uptake and retrograde transport of exogenous proteins in the hypoglossal nerve. Brain Res.32, 399–406 (1971)
LaVail, J. H.: Retrograde cell degeneration and retrograde transport techniques. Ch. 10, pp. 217–248. In: The use of axonal transport for studies of neuronal connectivity, W. M. Cowan and M. Cuénod (eds.). Amsterdam: Elsevier 1974
LaVail, J. H., LaVail, M. W.: The retrograde intraaxonal transport of horseradish peroxidase in the chick visual system: a light and electron microscopic study. J. Comp. Neurol.157, 303–358 (1974)
LaVail, J. H., Winston, K. R., Tish, A.: A method based on retrograde intraaxonal transport of protein for identification of cell bodies of origin of axons terminating within the central nervous system. Brain Res.58, 470–477 (1973)
Lund, R. D.: Development and plasticity of the brain, New York: Oxford University Press 1978
Lynch, G., Smith, R. L., Mensah, P., Cotman, C.: Tracing the dentate gyrus mossy fibre system with horseradish peroxidase histochemistry. Exp. Neurol.40, 516–524 (1973)
Mellick, R., Cavanagh, J. B.: Changes in blood vessel permeability during degeneration and regeneration in peripheral nerves. Brain91, 141–160 (1968)
Oldfield, B. J., McLachlan, E. M.: Uptake and retrograde transport of horseradish peroxidase by axons of intact and damaged peripheral nerve trunks. Neurosci. Lett.6, 135–141 (1977)
Olsson, T. P., Forsberg, I., Kristensson, K.: Uptake and retrograde axonal transport of horseradish peroxidase in regenerating facial motor neurons of the mouse. J. Neurocytol.7, 323–336 (1978)
Olsson, Y.: Studies on vascular permeability in peripheral nerves. Part 1. Distribution of circulating fluorescent serum albumin in normal, crushed and sectioned rat sciatic nerve. Acta Neuropathol. (Berl.)7, 1–15 (1966)
Olsson, Y.: The involvement of vasa nervorum in diseases of peripheral nerves. Ch. 24, pp. 644–664. In: Handbook of clinical neurology, Vol. 12. (ed.) P. J. Vinken and G. W. Bruyn. Amsterdam: North-Holland 1972
Olsson, Y., Kristensson, K.: The perineurium as a diffusion barrier to protein tracers following trauma to nerves. Acta Neuropathol. (Berl.)23, 105–111 (1973)
Schwab, M., Thoenen, H.: Retrograde axonal and transsynaptic transport of macromolecules: Physiological and pathophysiological importance. Agents Actions7, 361–368 (1977)
Sparrow, J. R.: Uptake and retrograde transport of horseradish peroxidase (HRP) by regenerating axons. Anat. Rec.190, 548 (1978)
Stockel, K., Schwab, M., Thoenen, H.: Comparison between retrograde axonal transport of nerve growth factor and tetanus toxin in motor, sensory and adrenergic neurons. Brain Res.99, 1–16 (1975)
Stockel, K., Thoenen, H.: Retrograde axonal transport of nerve growth factor: specificity and biological significance. Brain Res.85, 337–341 (1975)
Tischner, K.: Uptake of horseradish peroxidase by sensory nerve fibres in vitro. J. Anat.124, 83–97 (1977)
Watson, W. E.: Some metabolic responses of axotomized neurons to contact between their axons and denervated muscle. J. Physiol. (Lond.)210, 321–343 (1970)
Winkelmann, R. K., Schmit, R. W.: A simple silver method for nerve axoplasm. Proc. Staff Mtgs Mayo Clinic32, 217–222 (1957)
Yamada, K. M., Spooner, B. S., Wessells, N. K.: Ultrastructure and function of growth cones and axons of cultured nerve cells. J. Cell Biol.49, 614–635 (1971)
Zar, J. N.: Biostatistical analysis. Englewood Cliffs, N. Y.: Prentice-Hall 1974
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Sparrow, J.R., Kiernan, J.A. Uptake and retrograde transport of proteins by regenerating axons. Acta Neuropathol 47, 39–47 (1979). https://doi.org/10.1007/BF00698271
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DOI: https://doi.org/10.1007/BF00698271