Acta Neuropathologica

, Volume 89, Issue 3, pp 209–218 | Cite as

Axonal regeneration into chronically denervated distal stump

1. Electron microscope studies
  • V. Vuorinen
  • J. Siironen
  • M. Röyttä
Regular Paper

Abstract

In this study, we have analyzed the ability of axons to regenerate into chronically denervated peripheral nerve. As an experimental rat model, the proximal end of a newly transected rat tibial nerve was sutured into chronically denervated (3 months up to 16 months) common peroneal nerve. Samples for morphological studies were collected 3 and 6 weeks after anastomosis of the tibial and common peroneal nerves. Our results showing a distinct organization of the endoneurial matrix in the chronically denervated distal stumps conformed with those from previous studies. Long cytoplasmic processes of endoneurial fibroblasts in close contact with collagen fibrils (with a diameter of 50–60 nm) surrounded areas of thin collagen fibrils (with a diameter of 25–30 nm). Remnants of Schwann cell columns (i.e., bands of Büngner) were situated in areas of thin collagen fibrils. After 12 months of denervation the majority of the Schwann cells columns were replaced by thin collagen fibrils. Successful axonal regeneration was noted in distal stumps that had been denervated for 14 and even 16 months. However, axonal regeneration diminshed with prolonged denervation. The regenerating axons grew through the areas of thin collagen fibrils. The maturation and thickening of the regenerated axonal sprouts resulted in a decrease in areas of thin collagen fibrils. These results suggest that a chronically denervated nerve stump has the capacity to meet regenerating axons even after 16 months of deneravation, although the progressive atrophy of Schwann cell columns impairs the liklihood of good axonal regeneration. The areas of thin collagen fibrils may act as a ‘plastic’ bed for successful axonal regeneration, and a study of these fibrils may provide further insight into the role of the extracellular matrix during peripheral nerve regeneration.

Key words

Nerve repair Endoneurial cells Collagen Axonal sprouts Denervation 

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References

  1. 1.
    Abercromble M, Johnson ML (1946) The effect of reinnervation on collagen formation in regenerating sciatic nerve of rabbits. J Neurol Neurosurg Psychiatry 10:89–92Google Scholar
  2. 2.
    Anderson PN, Nadim W, Turmaine M (1991) Schwann cell migration through freeze-killed peripheral nerve grafts without accompanying axons. Acta Neuropathol 82:193–199Google Scholar
  3. 3.
    Brodsky B, Eikenberry E (1985) Supramolecular collagen assemblies. Ann NY Acad Sci 460:73–84Google Scholar
  4. 4.
    Bunge RP, Bunge MB (1978) Evidence that contact with connective tissue matrix is required for normal interaction between Schwann cells and nerve fibers. J Cell Biol 78:943–950Google Scholar
  5. 5.
    Dyck PJ, Lais A, Karnes J, Sparks M, Dyck PJB (1985) Peripheral axotomy induces neurofilament decrease, atrophy demyelination and degeneration of root and fasciculus gracilis fibers. Brain Res 340:19–36Google Scholar
  6. 6.
    Eather TF, Pollock M (1987) Collagen synthesis in axotomized peripheral nerve: evidence against Schwann cell involvement. Exp Neurol 96:214–218Google Scholar
  7. 7.
    Hachisuka K, Lais AC, Dyck PJ (1989) Ultrastructural alterations of primary afferent axons in the nucleus gracilis after peripheral nerve axotomy. J Neuropathol Exp Neurol 48:413–424Google Scholar
  8. 8.
    Hall SM (1986) Regeneration in cellular and acellular autografts in the peripheral nervous system. Neuropathol Appl Neurobiol 12:27–46Google Scholar
  9. 9.
    Hall SM (1989) Regeneration in the peripheral nervous system. Neuropathol Appl Neurobiol 15:513–529Google Scholar
  10. 10.
    Henkel W, Glanville RW (1982) Covalent crosslinking between molecules of type I and type III collagen. Eur J Biochem 122:205–213Google Scholar
  11. 11.
    Ide C, Tohyama K, Yokota R, Nitatori T, Onodera S (1983) Schwann cell basal lamina and nerve regeneration. Brain Res 288:61–75Google Scholar
  12. 12.
    Kallio PK, Vastamäki M (1992) An analysis of the results of late reconstruction of 132 median nerves. J Hand Surg [Br] 18:97–105Google Scholar
  13. 13.
    Kempe JL (1970) Surgery of peripheral nerves. A. Principles of peripheral nerve surgery. In: Kempe JL (ed) Operative neurosurgery, 1st edn. Springer-Verlag, Heidelberg pp 149–153Google Scholar
  14. 14.
    Kim DH, Conolly SE, Gillespie JT, Voorhies RM, Kline DG (1991) Electrophysiological studies of various graft lengths and lesion lengths in repair of nerve gaps in primates. J Neurosurg 76:440–446Google Scholar
  15. 15.
    Kim DH, Conolly SE, Kline DG, Voorhies RM, Smith A, Powell M, Yoes T, Daniloff JK (1994) Labeled Schwann cell transplants versus sural nerve grafts in nerve repair. J Neurosurg 80:254–260Google Scholar
  16. 16.
    Lapiere CM, Nusgens B, Pierard GE (1977) Interaction between collagen type I and type III in conditioning bundles organization. Connect Tissue Res 5:21–29Google Scholar
  17. 17.
    Lieberman AR (1971) The axon reaction: a review of principal features of perikaryal responses to axon injury. Int Rev Neurobiol 14:49–124Google Scholar
  18. 18.
    McGillicuddy JE (1985) Techniques of nerve repair. In: Wilkins RH, Rengachary SS (eds) Neurosurgery, 1st edn. McGraw-Hill, Hamburg, pp 1871–1880Google Scholar
  19. 19.
    Merle M, Amend P, Cour C, Foucher G, Michon J (1986) Microsurgical repair of peripheral nerve lesions. A study of 150 injuries of the median and ulnar nerves. Periph Nerve Repair Regener 2:17–26Google Scholar
  20. 20.
    Millesi H, Meissl G, Berger A (1972) The interfascicular nervegrafting of the medium and ulnar nerve. J Bone Joint Surg Am 54:727–750Google Scholar
  21. 21.
    Montero-Menei CN, Pouplard-Barthelaix A, Gumpel M, Baron-Van Evercooren A (1992) Pure Schwann cell suspension grafts promote regeneration of the lesioned septo-hippocampal cholinergic pathway. Brain Res 570:198–208Google Scholar
  22. 22.
    Mumenthaler M, Schliack H (1991) Principles of the treatment of peripheral nerve lesion. In: Mumenthaler M, Schliack H (eds) Peripheral Nerve Lesions, 5th edn. Georg Thieme Verlag, Stuttgart, pp 95–107Google Scholar
  23. 23.
    Nadim W, Anderson PN, Turmaine M (1990) The role of Schwann cells and basal lamina tubes in the regeneration of axons through long lengths of freeze killed nerve grafts. Neuropathol Appl Neurobiol 16:411–421Google Scholar
  24. 24.
    Ochoa J (1971) The sural nerve of human fetus: electron microscope observations and counts of axons. J Anat 108:231–245Google Scholar
  25. 25.
    Parry DAD, Craig AS (1984) Growth and development of collagen fibrils in connective tissue. In: Ruggeri A, Motta PM (eds) Ultrastructure of the connective tissue matrix, 1st edn. Martinus Nijhoff, Boston, pp 34–64Google Scholar
  26. 26.
    Pellegrino RG, Spencer PS (1985) Schwann cell mitosis in response to regenerating peripheral nerve axons in vivo. Brain Res 341:16–25Google Scholar
  27. 27.
    Röyttä M, Salonen V (1988) Long-term endoneurial changes after nerve transection. Acta Neuropathol 76:35–45Google Scholar
  28. 28.
    Röyttä M, Raine CS, Horwitz SB (1984) Taxol-induced neuropathy, short-term effects of local injection. J Neurocytol 13:685–701Google Scholar
  29. 29.
    Röyttä M, Salonen V, Peltonen J (1987) Reversible endoneurial changes after nerve injury. Acta Neuropathol (Berl) 73:323–329Google Scholar
  30. 30.
    Salonen V, Lehto M, Vahėri A, Aro H, Peltonen J (1985) Endoneurial fibrosis following nerve transection; an immunohistological study of collagen types and fibronectin in the rat. Acta Neuropathol (Berl) 67:315–321Google Scholar
  31. 31.
    Salonen V, Röyttä M, Peltonen J (1987) The effects of nerve transection on the endoneurial collagen fibril sheaths. Acta Neuropathol 74:13–21Google Scholar
  32. 32.
    Schröder JM (1968) Die Hyperneurotisation Büngnerscher Bänder bei der experimentellen Isoniazid-Neuropathie: Phasenkontrast- und elektronenmikroskopische Untersuchungen. Virchow Arch [B] 1:131–156Google Scholar
  33. 33.
    Schröder JM, Seiffert KE (1970) Die Feinstruktur der neuromatösen Neurotisation von Nerventransplantaten. Virchows Arch [B] 5:219–235Google Scholar
  34. 34.
    Siironen J, Sandberg M, Vuorinen V, Röyttä M (1992) Expression of type I and III collagens and fibronectin after transection of rat sciatic nerve. Lab Invest 67:80–87Google Scholar
  35. 35.
    Siironen J, Sandberg M, Vuorinen V, Röyttä M (1992) Laminin B1 and collagen type IV gene expression in transected peripheral nerve: reinnervation compared to denervation. J Neurochem 59:2184–2192Google Scholar
  36. 36.
    Siironen J, Vuorinen V, Taskinen HS, Röyttä M (1995) Axonal regeneration into chronically denervated distal stump. 2. Active expression of type I collagen mRNA in epineurium. Acta Neuropathol 89:219–226Google Scholar
  37. 37.
    Sjöberg J, Kanje M, Edström A (1988) Influence of nonneuronal cells on regeneration of the rat sciatic nerve. Brain Res 453:221–226Google Scholar
  38. 38.
    Sunderland S (1968) Degeneration of axon and associated changes. In: Sunderland (ed) Nerve and nerve injuries, 1st edn. Livingstone, London, p 82Google Scholar
  39. 39.
    Thomas PK (1964) Changes in the endoneurial sheaths of peripheral myelinated nerve fibers during Wallerian degeneration. J Anat 98:175–182Google Scholar
  40. 40.
    Torvik A (1976) Central chromatolysis and the axon reaction, a reappraisal. Neuropathol Appl Neurobiol 2:423–432Google Scholar
  41. 41.
    Wang GY, Hirai KI, Shimada H (1992) The role of laminin, a component of Schwann cell basal lamina, in rat sciatic nerve regeneration within antiserum-treated nerve grafts. Brain Res 570:116–125Google Scholar
  42. 42.
    Weinberg HJ, Spencer PS (1978) The fate of Schwann cells isolated from axonal contact. J Neurocytol 7:555–569Google Scholar

Copyright information

© Springer-Verlag 1995

Authors and Affiliations

  • V. Vuorinen
    • 1
  • J. Siironen
    • 2
    • 3
  • M. Röyttä
    • 2
    • 3
  1. 1.Department of NeurosurgeryUniversity Hospital of HelsinkiHelsinkiFinland
  2. 2.Department of PathologyUniversity of TurkuTurkuFinland
  3. 3.Central HospitalUniversity of TurkuTurkuFinland

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