Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Fine structural and immunohistochemical identification of perineurial cells connecting proximal and distal stumps of transected peripheral nerves at early stages of regeneration in silicone tubes

  • 98 Accesses

  • 19 Citations

Abstract

Perineurial cells are specialized connective tissue cells that form a barrier between endoneurium and epineurium in normal nerves. In the present study, the formation of the perineurium after transection of rat sciatic nerves was investigated. The cord bridging the gap between proximal and distal stumps through silicone tubes was studied 3, 7, 12, 18, and 21 days after surgery using electron microscopy and antibodies against epithelial membrane antigen (EMA), a marker for perineurial cells that has thus far not been applied to the study of differentiating cells in nerve tubulation systems. Initially, a thin cord consisting of fibrin bridged the gap between the stumps. At 7 days, longitudinal cells had migrated from both stumps toward the center of the tubes on the surface of the fibrin cord. These cells were immunoreactive with anti-EMA. At 12 days, ultrastructural features of perineurial cells (desmosomes, tight junctions, actin filaments with dense bodies, tonofilaments) were prominent in these cells. Subsequently, the gap was bridged through the perineurial tube by endothelial cells, pericytes, fibroblasts, Schwann cells, and axons. At 21 days, a single large nerve fascicle ensheathed by a mature perineurium was found between the stumps. Thus, the first cells to connect proximal and distal stumps in the investigated nerve regeneration silicon chamber system are perineurial cells. Through the tube formed by these cells, blood vessels and nerve fibers bridge the gap. Therefore, establishment of a perineurial connection between nerve stumps appears to be important in the sequence of events during nerve regeneration.

This is a preview of subscription content, log in to check access.

References

  1. 1.

    Ariza A, Bilbao JM, Rosai J (1988) Immunohistochemical detection of epithelial membrane antigen in normal perineurial cells and perineurioma. Am J Surg Pathol 12: 678–683

  2. 2.

    Bunge MB, Wood PM, Tynan LB, Banes JR (1989) Perineurium orginates from fibroblasts: demonstration in vitro with a retroviral marker. Science 243: 229–231

  3. 3.

    Burkel WE (1967) The histological fine structure of perineurium. anat Rec 158: 177–190

  4. 4.

    Hirose T, Sumitomo M, Kudo E, Hasegawa T, Teramae T, Murase M, Higasa Y, Ikata T, Hizawa K (1989) Malignant peripheral nerve sheath tumor (MPNST) showing perineurial cell differentiation. Am J Surg Pathol 13: 613–620

  5. 5.

    Klemm H (1970) Das Perineurium als Diffusionsbarriere gegenüber Peroxydase bei epi- und endoneuraler Applikation. Z Zellforsch 108: 431–445

  6. 6.

    Lehmann RAW, Hayes GJ (1967) Degeneration and regeneration in peripheral nerve. Brain 90: 285–296

  7. 7.

    Liu HM (1992) The role of extracellular matrix in peripheral nerve regeneration: a wound chamber study. Acta Neuropathol 83: 469–474

  8. 8.

    Longo FM, Manthorpe M, Skaper SD, Lundborg G, Varon S (1983) Neuronotrophic activities accumulated in vivo within silicone nerve regenerating chambers. Brain Res 261: 107–117

  9. 9.

    Lundborg G, Gelberman RH, Longo FM, Powell HC, Varon S (1982) In vivo regeneration of cut nerves encased in silicone tubes. Growth across a six-millimeter gap. J Neuropathol Exp Neurol 41: 412–422

  10. 10.

    Obst T (1971) Über das Endgebiet des Perineuriums an den Zahnnerven der Ratte. Z Zellforsch 114: 515–531

  11. 11.

    Olsson Y, Kristensson K (1973) The perineurium as a diffusion barrier to protein tracers following trauma to nerves. Acta Neuropathol (Berl) 23: 105–111

  12. 12.

    Perentes E, Nakagawa Y, Ross GW, Stanton C, Rubinstein LJ (1987) Expression of epithelial membrane antigen in perineurial cells and their derivatives. An immunohistochemical study with multiple markers. Acta Neuropathol (Berl) 75: 160–165

  13. 13.

    Politis MJ, Ederle K, Spencer PS (1982) Tropism in nerve regeneration in vivo. Attraction of regenerating axons by diffusible factors derived from cells in distal nerve stumps of transected peripheral nerves. Brain Res 253: 1–12

  14. 14.

    Rich KM, Alexander TD, Pryor JC, Hollowell JP (1989) Nerve growth factor enhances regeneration through silicone chambers. Exp Neurol 105: 162–170

  15. 15.

    Scaravilli F (1984) Regeneration of the perineurium across a surgically induced gap in a nerve encased in a plastic tube. J Anat 139: 411–424

  16. 16.

    Schröder JM, Seiffert KE (1970) Die Feinstruktur der neuromatösen Neurotisation von Nerventransplantaten. Virchows Arch [B] 5: 219–235

  17. 17.

    Schröder JM, May R, Weis J (1993) Perineurial cells are the first to traverse gaps of peripheral nerves in silicon tubes. Clin Neurol Neurosurg 95: S78-S83

  18. 18.

    Sunderland S (1977) Nerves and nerve injuries. Churchill Livingstone, Edinburgh

  19. 19.

    Theaker JM, Gatter KC, Puddle J (1988) Epithelial membrane antigen expression by the perineurium of the peripheral nerve and in peripheral nerve tumors. Histopathology 13: 171–179

  20. 20.

    Thomas PK, Bhagat S (1978) The effect of extraction of the intrafascicular contents of peripheral nerve trunks on perineurial structure. Acta Neuropathol (Berl) 43: 135–141

  21. 21.

    Thomas PK, Jones DG (1967) The cellular response to nerve injury. 2. Regeneration of the perineurium after nerve section. J Anat 101: 45–55

  22. 22.

    Thomas PK, Berthold C-H, Ochoa J (1992) Microscopic anatomy of the peripheral nervous system. Nerve trunks and spinal roots. In: Dyck PJ, Thomas PK: Peripheral neuropathy. WB Saunders, Philadelphia, pp 28–35

  23. 23.

    Weis J, Schröder JM (1989) Differential effects of nerve, muscle, and fat tissue on regenerating nerve fibers in vivo. Muscle Nerve 12: 723–734

  24. 24.

    Weis J, Schröder JM (1989) The influence of fat tissuc on neuroma formation. J Neurosurg 71: 588–593

  25. 25.

    Weis J, Fine SM, David C, Savarirayan S, Sanes JR (1991) Integration site-dependent expression of a transgene reveals specialized features of cells associated with neuromuscular junctions. J Cell Biol 113: 1385–1397

  26. 26.

    Weis J, Alexianu ME, Heide G, Schröder JM (1993) Renaut bodies contain elastic fiber components. J Neuropathol Exp Neurol 52: 444–451

  27. 27.

    Weis J, May R, Schröder JM (1993) Formation of a perineurial tube between proximal and distal nerve stumps in nerve regeneration chambers. Clin Neuropathol 5: 277

  28. 28.

    Weiss PD, Taylor AC (1944) Further experimental evidence against ‘neurotropism’ in nerve regeneration. J Exp Zool 95: 233–257

  29. 29.

    Williams LR, Longo FM, Powell HC Lundborg G, Varon S (1983) Spatial-temporal progress of peripheral nerve regeneration within a silicone chamber: parameters for a bioassay. J Comp Neurol 218: 460–470

Download references

Author information

Correspondence to J. Michael Schröder.

Additional information

The results of this study were presented in part at the Post Graduate Boerhaave Course: Brachial Plexus Injury, Leyden, March 25 and 26, 1993 [17] and at the 38th Annual Meeting of the Deutsche Gesellschaft für Neuropathologie and Neuroanatomie, Berlin, October 6–9, 1993 [27]

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Weis, J., May, R. & Schröder, J.M. Fine structural and immunohistochemical identification of perineurial cells connecting proximal and distal stumps of transected peripheral nerves at early stages of regeneration in silicone tubes. Acta Neuropathol 88, 159–165 (1994). https://doi.org/10.1007/BF00294509

Download citation

Key words

  • Perineurial cells
  • Nerve regeneration
  • Immunohistochemistry
  • Epithelial membrane antigen