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The expression of nerve growth factor receptor on Schwann cells and the effect of these cells on the regeneration of axons in traumatically injured human spinal cord

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Abstract

To investigate the effects of Schwann cells and nerve growth factor receptor (NGFR) on the regeneration of axons, autopsy specimens of spinal cord from 21 patients with a survival time of 2 h to 54 years after spinal cord trauma were studied using immunohistochemistry and electron microscopy. Regenerating sprouts of axons could be observed as early as 4 days after trauma. At 4.5 months after trauma, many regenerating nests of axons appeared in the injured spinal cord. The regeneration nests contained directionally arranged axons and Schwann cells. Some axons were myelinated. In injured levels of the spinal cord, the Schwann cells exhibited an increased expression of NGFR within spinal roots. These results show that an active regeneration process occurs in traumatically injured human spinal cord. The NGFR expressed on Schwann cells could mediate NGF to support and induce the axon regeneration in the central nervous system.

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References

  1. Barbacid M (1994) The trk family of neurotrophin receptors. J Neurobiol 25: 1386–1403

    Article  PubMed  CAS  Google Scholar 

  2. Bixby JL, Lilien J, Reichardt LF (1988) Identification of the major proteins that promote neuronal process outgrowth on Schwann cells in vitro. J Cell Biol 107: 353–361

    Article  PubMed  CAS  Google Scholar 

  3. Björklund A, Stenevi U (1979) Regeneration of monoaminergic and cholinergic neurons in the mammalian central nervous system. Physiol Rev 59: 62–100

    PubMed  Google Scholar 

  4. Blakemore WF (1978) Observations on remyelination in the rabbit spinal cord following demyelination induced by lysolecithin. Neuropathol Appl Neurobiol 4: 47–59

    Article  PubMed  CAS  Google Scholar 

  5. Blight AR (1994) Effects of silica on the outcome from experimental spinal cord injury: implication of macrophages in secondary tissue damage. Neuroscience 60: 263–273

    Article  PubMed  CAS  Google Scholar 

  6. Blight AR, Saito K, Heyes MP (1993) Increased levels of the excitotoxin quinolinic acid in spinal cord following contusion injury. Brain Res 632: 314–316

    Article  PubMed  CAS  Google Scholar 

  7. Bothwell M (1991) Keeping track of neurotrophin receptors. Cell 65: 915–918

    Article  PubMed  CAS  Google Scholar 

  8. Caroni P, Schwab ME (1988) Two membrane protein fractions from rat central myelin with inhibitory properties for neurite growth and fibroblast spreading. J Cell Biol 106: 1281–1288

    Article  PubMed  CAS  Google Scholar 

  9. Dusart I, Isacson O, Nothias F, Gumpel M, Peschanski M (1989) Presence of Schwann cells in neurodegenerative lesions of the central nervous system. Neurosci Lett 105: 246–250

    Article  PubMed  CAS  Google Scholar 

  10. Dusart I, Marty S, Peschanski M (1992) Demyelination, and remyelination by Schwann cells and oligodendrocytes after kainate-induced neuronal depletion in the central nervous system. Neuroscience 51: 137–148

    Article  PubMed  CAS  Google Scholar 

  11. Farooqui AA, Horrocks LA (1994) Involvement of glutamate receptors, upases, and phospholipases in long-term potentiation and neurodegeneration. J Neurosci Res 38: 6–11

    Article  PubMed  CAS  Google Scholar 

  12. Galandiuk S, Raque G, Appel S, Polk HC Jr (1993) The twoedged sword of large-dose steroids for spinal cord trauma. Ann Surg 218: 419–427

    Article  PubMed  CAS  Google Scholar 

  13. Gold BG, Mobley WC, Matheson SF (1991) Regulation of axonal caliber, neurofilament content, and nuclear localization in mature neurons by nerve growth factor. J Neurosci 11: 943–955

    PubMed  CAS  Google Scholar 

  14. Haghighi SS, Hall ED, Geng XZ, Oro JJ, Johnson GC (1993) Therapeutic value of 21-aminosteroid U74389F in acute spinal cord injury. Neurol Res 15: 321–326

    PubMed  CAS  Google Scholar 

  15. Haghighi SS, Perez-Espejo A, Geng XZ, Padratzik J, Oro JJ, Spollen L (1994) Effect of 21-aminosteroid pretreatment in compression trauma to the spinal cord. Neurol Res 16: 268–272

    PubMed  CAS  Google Scholar 

  16. Hempstead BL, Martin-Zanca D, Kaplan DR, Parada LF, Chao MV (1991) High-affinity NGF binding requires coexpression of trk proto-oncogene and the low-affinity NGF receptor. Nature 350: 678–683

    Article  PubMed  CAS  Google Scholar 

  17. Iwai A, Monafo WW, Eliasson SG (1993) Methylprednisolone treatment of experimental spinal cord injury. Paraplegia 31: 417–429

    PubMed  CAS  Google Scholar 

  18. Jessen KR, Mirsky R, Morgan L (1987) Myelinated, but not unmyelinated axons, reversibly down regulate N-CAM in Schwann cells. J Neurocytol 16: 681–688

    Article  PubMed  CAS  Google Scholar 

  19. Johnson EM, Taniuchi JR, DiStefano PS (1988) Expression and possible function of nerve growth factor receptors in Schwann cells. Trends Neurosci 11: 299–304

    Article  PubMed  CAS  Google Scholar 

  20. Koliatsos VE, Crawford TO, Price DL (1991) Axotomy induces nerve growth factor receptor immunoreactivity in spinal motor neurons. Brain Res 549: 297–304

    Article  PubMed  CAS  Google Scholar 

  21. Kromer LF, Cornbrooks CJ (1985) Transplants of Schwann cell cultures promote axonal regeneration in the adult mammalian brain. Proc Natl Acad Sci USA 82: 6330–6334

    Article  PubMed  CAS  Google Scholar 

  22. Lee KF, Huber LJ, Landis SC, Sharpe AH, Chao MV, Jaenisch R (1992) Targeted mutation of the gene encoding the low affinity NGF receptor p75 leads to deficits in the peripheral sensory nervous system. Cell 69: 737–749

    Article  PubMed  CAS  Google Scholar 

  23. Letourneau PC, Shattuck TA, Roche FK, Takeichi M, Lemmon V (1990) Nerve growth cone migration onto Schwann cells involves the calcium-dependent adhesion molecule, N-Cadherin. Dev Biol 138: 430–442

    Article  PubMed  CAS  Google Scholar 

  24. Martini R, Schachner M (1988) Immunoelectron microscopic localization of neural cell adhesion molecules (L1, N-CAM, and myelin associated glycoprotein) in regenerating adult mouse sciatic nerve. J Cell Biol 106: 1735–1746

    Article  PubMed  CAS  Google Scholar 

  25. Neuberger TJ, Cornbrooks CJ, Kromer LF (1992) Effects of delayed transplantation of cultured Schwann cells on axonal regeneration from central nervous system cholinergic neurons. J Comp Neurol 315: 16–33

    Article  PubMed  CAS  Google Scholar 

  26. Popovich PG, Reinhard JF Jr, Flanagan EM, Stokes BT (1994) Elevation of the neurotoxin quinolinic acid occurs following spinal trauma. Brain Res 633: 348–52

    Article  PubMed  CAS  Google Scholar 

  27. Qu ZX, Xu J, Hogan EL, Hsu CY (1993) Effect of U-50488 h, a selective opioid kappa receptor agonist, on vascular injury after spinal cord trauma. Brain Res 626: 45–49

    Article  PubMed  CAS  Google Scholar 

  28. Reier PJ, Eng LF, Jakeman L (1989) Reactive astrocyte and axonal outgrowth in the injured CNS: is gliosis really an impediment to regeneration? In: Seil FJ (ed) Neural regeneration and transplantation. Liss, New York, pp 183–209

    Google Scholar 

  29. Rende M, Hagg T, Manthorpe M, Varon S (1992) Nerve growth factor receptor immunoreactivity in neurons of the normal adult rat spinal cord and its modulation after peripheral nerve lesions. J Comp Neurol 319: 285–298

    Article  PubMed  CAS  Google Scholar 

  30. Schwab ME (1990) Myelin-associated inhibitors of neurite growth. Exp Neurol 109: 2–5

    Article  PubMed  CAS  Google Scholar 

  31. Seilheimer B, Schachner M (1988) Studies of adhesion molecules mediating interactions between cells of peripheral nervous system indicate a major role for L1 in mediating sensory neuron growth on Schwann cells in culture. J Cell Biol 107: 341–353

    Article  PubMed  CAS  Google Scholar 

  32. Sharma HS, Olsson Y, Cervos-Navarro J (1993) p-Chlorophenylalanine, a serotonin synthesis inhibitor, reduces the response of glial fibrillary acidic protein induced by trauma to the spinal cord. An immunohistochemical investigation in the rat. Acta Neuropathol 86: 422–427

    Article  PubMed  CAS  Google Scholar 

  33. Sharma HS, Olsson Y, Nyberg F, Dey PK (1993) Prostaglandins modulate alterations of microvascular permeability, blood flow, edema and serotonin levels following spinal and injury: an experimental study in the rat. Neuroscience 57: 443–449

    Article  PubMed  CAS  Google Scholar 

  34. Snider WD (1994) Functions of the neurotrophins during nervous system development: what the knockouts are teaching us. Cell 77: 627–638

    Article  PubMed  Google Scholar 

  35. Wang ZH, Gerhard L (1995) Reexpression of nerve growth factor receptor on motoneurons and axon in human traumatically injured spinal cord. Chin Med J 108: 1–5

    Google Scholar 

  36. Wrathall JR, Choiniere D, Teng YD (1994) Dose-dependent reduction of tissue loss and functional impairment after spinal cord trauma with the AMPA/kainate antagonist NBQX. J Neurosci 14: 6598–6607

    PubMed  CAS  Google Scholar 

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Wang, Z.H., Walter, G.F. & Gerhard, L. The expression of nerve growth factor receptor on Schwann cells and the effect of these cells on the regeneration of axons in traumatically injured human spinal cord. Acta Neuropathol 91, 180–184 (1996). https://doi.org/10.1007/s004010050411

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  • DOI: https://doi.org/10.1007/s004010050411

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