Journal of Neurocytology

, Volume 16, Issue 5, pp 701–711 | Cite as

Expression of growth factor receptors in injured nervous tissue. II. Induction of specific platelet-derived growth factor binding in the injured PNS is associated with a breakdown in the blood-nerve barrier and endoneurial interstitial oedema

  • Gennadij Raivich
  • Georg W. Kreutzberg


We have studied the expression of the platelet-derived growth factor (PDGF) receptors in the injured chick PNS using [125I]-iodinated PDGF as a radioactive probe to map autoradiographically thein situ distribution of specific [125I]PDGF binding.

Crush or transection of the sciatic nerve led to a rapid and massive induction of specific [125I]PDGF binding on fibroblast-like cells of the injured endoneurium, already observed 2 h postoperatively. It is initially characterized by a symmetrical appearance both below and above the site of injury, spreading throughout the distal part of the lesioned nerve 1 to 2 days postoperatively. Comparison with distribution of specific [125I]β-nerve growth factor (β-NGF) binding (see preceding paper) revealed a number of important differences: unlike the specific [125I]β-NGF binding, which rapidly disappears after reinnervation of the distal nerve, this was not observed in the case of [125I]PDGF binding. [125I]PDGF binding also correlated poorly with the extent of axonal injury. The segmental removal of the perineurium, resulting in heavy interstitial oedema without widespread axonal injury, led to a strong, local induction of [125I]PDGF binding, while causing moderate β-NGF binding to only the few degenerating nerve fibre tubes. These results suggest the existence of different pathophysiological mechanisms that regulate the expression of PDGF and β-NGF receptors in the lesioned and regenerating PNS.


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  1. Antoniades, H. N., Scher, C. D. &Stiles, C. D. (1979) Purification of human platelet-derived growth factor.Proceedings of the National Academy of Sciences USA 76, 1809–13.Google Scholar
  2. Antoniades, H. N., Stathakos, D. &Scher, C. D. (1975) Isolation of a cationic polypeptide from human serum that stimulates proliferation of 3T3 cells.Proceedings of the National Academy of Sciences USA 76, 1809–13.Google Scholar
  3. Bowen-Pope, D. F. &Ross, R. (1982) Platelet-derived growth factor: II. Specific binding to cultured cells.Journal of Biological Chemistry 257, 5161–71.Google Scholar
  4. Bowen-Pope, D. F., Seifert, R. A. &Ross, R. (1985) The platelet-derived growth factor receptor. InControl of Animal Cell Proliferation, Vol. I. (edited byBoynton, A. L. &Leffert, H. L.), pp. 281–312. New York: Academic Press.Google Scholar
  5. Collins, T., Ginsburg, D., Boss, J. M., Orkin, S. H. &Pober, J. S. (1985) Cultured human endothelial cells express platelet-derived growth factor B-chain: cDNA cloning and structural analysis.Nature 316, 748–50.Google Scholar
  6. Folkman, J. (1982) Angiogenesis: initiation and control.Annals of New York Academy of Science 401, 212–27.Google Scholar
  7. Haftek, J. &Thomas, P. K. (1968) Electron-microscope observations on the effects of localized crush injuries on the connective tissues of the peripheral nerve.Journal of Anatomy 103, 233–43.Google Scholar
  8. Hassler, O. (1969) Vascular reactions after experimental nerve section, suture and transplantation.Acta neurologica scandinavica 45, 335–41.Google Scholar
  9. Heldin, C. H., Johnsson, A., Wennergren, S., Wenstedt, C., Betsholtz, C. &Westermark, B. (1986) A human osteosarcoma cell line secretes a growth factor structurally related to a homodimer of PDGF A-chains.Nature 319, 511–14.Google Scholar
  10. Heldin, C. H., Wasteson, A. &Westermark, B. (1977) Partial purification and characterization of platelet factors stimulating the multiplication of normal human glial cells.Experimental Cell Research 109, 429–37.Google Scholar
  11. Heldin, C. H., Westermark, B. &Wasteson, A. (1979) Platelet derived growth factor: purification and partial characterization.Proceedings of the National Academy of Sciences USA 76, 3722–6.Google Scholar
  12. Heldin, C. H., Westermark, B. &Wasteson, A. (1981) Specific receptors for platelet-derived growth factor on cells derived from connective tissue and glia.Proceedings of the National Academy of Sciences USA 78, 3664–8.Google Scholar
  13. Huang, J. S., Huang, S. S. &Deuel, T. F. (1984) Specific covalent binding of platelet-derived growth factor to human plasma alpha2-macroglobulin.Proceedings of the National Academy of Sciences USA 81, 342–6.Google Scholar
  14. Huang, J. S., Huang, S. S., Kennedy, B. &Deuel, T. (1982) Platelet-derived growth factor: specific binding to target cells.Journal of Biological Chemistry 257, 8130–6.Google Scholar
  15. Jaye, M., McConathy, E., Drohan, W., Tong, B., Deuel, T. &Maciag, T. (1985) Modulation of thesis gene transcript during endothelial cell differentiationin vitro.Science 228, 882–5.Google Scholar
  16. Jurecka, W., Ammerer, H. P. &Lassmann, H. (1975) Regeneration of transected peripheral nerve. An autoradiographic and electron microscopic study.Acta neuropathologica (Berlin) 32, 299–312.Google Scholar
  17. Leibovich, S. J. &Ross, R. (1976) A macrophage-dependant factor that stimulates the proliferation of fibroblastsin vitro.American Journal of Pathology 84, 501–13.Google Scholar
  18. Lemke, G. E. &Brockes, J. (1984) Identification and purification of glial growth factor.Journal of Neuroscience 4, 75–83.Google Scholar
  19. Martinet, Y., Bitterman, P. B., Mornex, J. F., Grotendorst, G. R., Martin, G. R. &Crystal, R. G. (1986) Activated human nonocytes express thec-sis proto-oncogene and release a mediator showing PDGF-like activity.Nature 319, 158–60.Google Scholar
  20. Mellick, R. S. &Cavanagh, J. B. (1968) Changes in blood vessel permeability during degeneration and regeneration in peripheral nerves.Brain 91, 141–60.Google Scholar
  21. Nukada, H. &Dyck, P. J. (1986) Neovascularization after ischemic nerve injury.Experimental Neurology 92, 391–7.Google Scholar
  22. Ohi, T., Poduslo, J. F., Curran, G. L. &Dyck, P. J. (1985) Quantitative method for detection of blood-nerve barrier alterations in experimental animal models of neuropathy.Experimental Neurology 90, 365–72.Google Scholar
  23. Olsson, Y. (1966) Studies on vascular permeability in peripheral nerves. Distribution of circulating fluorescent serum albumin in normal, crushed and sectioned rat sciatic nerve.Acta neuropathologica (Berlin) 7, 1–15.Google Scholar
  24. Olsson, Y. (1968) Topographical differences in the vascular permeability of the peripheral nervous system.Acta neuropathologica (Berlin) 10, 26–33.Google Scholar
  25. Raines, E. W., Bowen-Pope, D. F. &Ross, R. (1984) Plasma binding proteins for platelet-derived growth factor that inhibit its binding to cell-surface receptors.Proceedings of the National Academy of Sciences USA 81, 3424–8.Google Scholar
  26. Raivich, G. &Kreutzberg, G. W. (1987) Expression of growth factor receptors in injured nervous tissue. I. Axotomy leads to a shift in the cellular distribution of specific β-nerve growth factor binding in the injured and regenerating PNS.Journal of Neurocytology 16, 701–11.Google Scholar
  27. Ross, R., Glomset, J., Kariya, B. &Harker, L. (1974) A platelet-dependent serum factor that stimulates the proliferation of arterial smooth muscle.Proceedings of the National Academy of Sciences USA71, 1207–10.Google Scholar
  28. Shimokado, K., Raines, E. W., Madtes, D. K., Barrett, T. B., Benditt, E. P. &Ross, R. (1985) A significant part of macrophage-derived growth factor consists of at least two forms of PDGF.Cell 43, 277–86.Google Scholar
  29. Sparrow, J. R. &Kiernan, J. A. (1981) Endoneurial vascular permeability in degenerating and regenerating peripheral nerves.Acta neuropathologica (Berlin) 53, 181–8.Google Scholar
  30. Spencer, P. S., Weinberg, H. J., Raine, C. S. &Prineas, J. W. (1975) The perineurial window — a new model of focal demyelination and remyelination.Brain Research 96, 323–9.Google Scholar
  31. Taniuchi, M., Clark, H. B. &Johnson, E. M. (1986) Induction of nerve growth factor receptor in Schwann cells after axotomy.Proceedings of the National Academy of Sciences USA 83, 4094–8.Google Scholar
  32. Thomas, P. K. (1970) The cellular response to nerve injury. 3. The effect of repeated crush injuries.Journal of Anatomy 106, 463–70.Google Scholar
  33. Williams, L. T., Tremble, P. &Antoniades, H. N. (1982) Platelet derived growth factor binds specifically to receptors on vascular smooth muscle cells and the binding becomes nondissociable.Proceedings of the National Academy of Sciences USA 79, 5867–70.Google Scholar
  34. Witte, L. D., Kaplan, K. L., Nossel, H. L., Lages, B. A., Weiss, H. F. &Goodman, D. S. (1978) Studies of the release from human platelets of the growth factor for cultured human arterial smooth muscle cells.Circulation Research 42, 402–9.Google Scholar

Copyright information

© Chapman and Hall Ltd. 1987

Authors and Affiliations

  • Gennadij Raivich
    • 1
  • Georg W. Kreutzberg
    • 1
  1. 1.Department of NeuromorphologyMax-Planck Institute for PsychiatryMartinsriedGermany

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