Regeneration in the axotomized cord: influence of cyclosporine A and neonatal immune desensitization in mammals

  • G. Palladini
  • B. Caronti


Regeneration is a normai regulative process by which an organism reestablishes its lost equilibrium and restores, more or less completely, body parts that have been lost or severely injured. Repetitive regeneration indicates the renewal of cells, tissue and organs that have a shorter life then the whole organism itself, whereas the term reparative regeneration applies to the repair of damage after injury (Filoni, 1981).


Spinal Cord Spinal Cord Injury Axonal Regeneration Spinal Cord Lesion Mammalian Central Nervous System 
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  1. Aarli JA (1983) The immune system and nervous system, j Neurol 229: 137–154PubMedCrossRefGoogle Scholar
  2. Aari JA, Aparicio SR, Lumdsden CE, Tonder O (1975) Binding of normal human IgG to myelin sheats, glia and neurons. Immunology 28: 171–185Google Scholar
  3. Aubert I, Ridet JL, Gage FH (1995) Regeneration in the adult mammalian CNS: guided by development. Curr Opinion Neurobiol 5: 625–635CrossRefGoogle Scholar
  4. Bahr M, Bonhoeffer F (1994) Perspectives on axonal regeneration in the mammalian CNS. TINS 17: 473–479PubMedGoogle Scholar
  5. Benfey M, Aguayo AJ (1982) Extensive elongation of axon from rat brain into peripheral nerve graft. Nature (Lond) 296: 150–152CrossRefGoogle Scholar
  6. Bentivoglio M, Kuypers HGJM, Catsman-Berrevoets CE, Loewe H, Dann O (1980) Two new fluorescent retrograde neuronal tracers whichare transported over long distances. Neurosci Lett 18: 25–30PubMedCrossRefGoogle Scholar
  7. Bernstein JJ, Goldberg WJ (1995) Experimental spinal cord transplantation as a mechanism of spinal cord regeneration. Paraplegia 33: 250–253PubMedCrossRefGoogle Scholar
  8. Bernstein JJ, Wells MR (1980) Puromycine induction of transient regeneration in mammalian spinal cord. In: McConnel PS, Boer GJ, Romjin HJ, van de Pioli NE, Corner MA (eds) Adaptive capabilities of the nervous system. Prog Brain Res 53: 21–38Google Scholar
  9. Berry M (1979) Regeneration in central nervous system. In: Thomas Smith WT, Cavanagh JB (eds) Recent Advances in Neuropathology. Churchill-Livingstone, Edinburgh, pp 67–111Google Scholar
  10. Berry M, Riches AC (1974) An immunological approach to regeneration in central nervous system, Br Med Bull 30: 135–140PubMedGoogle Scholar
  11. Bjorklund A (1994) A question of making it work. Nature (Lond) 367: 112Google Scholar
  12. Borel JM, Feurer C, Guble HU, Stahelin H (1976) Biological effect of Cyclosporine A: a new anti-lymphocytic agent. Agents Actions 6: 468–475PubMedCrossRefGoogle Scholar
  13. Bowen FP (1986) Immunological reactions after cortical lesions in rabbits. Arch Neurol 19: 398–402CrossRefGoogle Scholar
  14. Bracken MB, Shepard MJ, Collins WF jr, Holford TR, Baskin DS, Eisenberg HM, Flamm E, Leo-Summers, Maroon JC, Marshall LF, Perot PL Jr, Piemeier J, Sonntag VKH, Wagner FC, Wildelger JL, Winn HR, Young W (1992) Methylprednisolone or naloxone treatment after acute spinal cord injury: 1 years follow-up data. J Neurosurg 76: 23–31PubMedCrossRefGoogle Scholar
  15. Bregman BS, Goldberger ME (1982) Anatomical plasticity and sparing of function after spinal cord damage in neonatal rats. Science 217: 553–555PubMedCrossRefGoogle Scholar
  16. Bregman BS, Goldberger ME (1983) Infant lesion effects. II. Sparing and recovery of function after spinal cord damage in newborn and adult rats. Dev Brain Res 9: 119–135Google Scholar
  17. Bregman BS, Kunkel-Badgen E, Reier PJ, Hai HD, McAtee M, Da G (1993) Recovery of function after spinal cord injury: mechanism underlying transplant-mediated recovery of function differ after spinal cord injury in newborn and adult rat. Exp Neurol 123: 3–16PubMedCrossRefGoogle Scholar
  18. Bullock TH, Horridge GA (1965) Structure and Function in the Nervous System of Invertebrates, Vol 1. Freeman, San Francisco, pp 108–109Google Scholar
  19. Butler EG, Ward MB (1967) Reconstitution of the spinal cord after ablation in adult Trituras. Dev Biol 15: 464–486PubMedCrossRefGoogle Scholar
  20. Caroni P, Schwab M (1988a) Two membrane protein fractions from rat central myelin with inhibitory properties from neurite growth and fibrobiast spreading. J Cell Biol 106: 1281–1288PubMedCrossRefGoogle Scholar
  21. Caroni P, Schwab M (1988b) Antibody against myelin-associated inhibitor of neurite growth neutralized nonpermissive substrates properties of CNS white matter. Neuron 1: 85–96PubMedCrossRefGoogle Scholar
  22. Chen D, Jhaveri S, Schneider GE (1995) Intrinsic changes in developing retinal neurons results in regenerative failure of their axons. Proc Natl Acad Sci USA 92: 7287–7291PubMedCrossRefGoogle Scholar
  23. Cohen AH, Baker MT, Dobrov TA (1988) Functional regeneration demonstrated in the adult spinal cord of lampreys. Soc Neurosci Abstract 14: 482–485Google Scholar
  24. Collins GH, West NR (1989) Prospects for axonal regrowth in spinal cord injury. Brain Res Bull 22: 89–92PubMedCrossRefGoogle Scholar
  25. David S, Aguayo AJ (1981) Axonal elongation into peripheral nervous system bridges after central nervous system injury in adult rat. Science 214: 931–933PubMedCrossRefGoogle Scholar
  26. Davies S, Illlis LS, Raisman G (1995) Regeneration in the central nervous system and related factors. Summary of the Bermuda Paraplegia Conference, 1994. Paraplegia 33: 10–17Google Scholar
  27. DeLaTorre JC, Johnson CM, Goode DJ, Mullan S (1975) Pharmacologie treatment and evaluation of permanent experimental spinal trauma. Neurology 25: 508–511CrossRefGoogle Scholar
  28. DeLaTorre JC (3984) Spinal cord injury models. Prog Neurobioi 4: 289–344Google Scholar
  29. Donatelle JM (1977) Growth of the corticospinal tracts and the development of placing reactionsin the postnatal life. J Comp Neurol 175: 207–232PubMedCrossRefGoogle Scholar
  30. Eitan S, Solomon A, Lavie V, Yoles E, Hirschberg DL, Belkin M, Schwartz M (1994) Recovery of visual response of injured adult rat optic nerves treated with transglutaminase. Science 264: 1764–1768PubMedCrossRefGoogle Scholar
  31. Fabrizi C, Caronti B, Palladini G (1995) Autoimmunity, central axonal regeneration and Cyciosporine A. In vitro observations on the action mechanism. Rend Fis Acc Lincei 6: 87–93CrossRefGoogle Scholar
  32. Fast DJ, Lynch R, Lau RW (3993) Cyciosporine A inhibit nitric oxide production by L529 cells in response to tumor necrosis factor and interferon. J Interferon Res 13: 235–240CrossRefGoogle Scholar
  33. Feringa EF, Wendt JS, Randall DJ (1974) Immunosuppressive treatment to enhance spinal cord regeneration in rats. Neurology 263: 287–293CrossRefGoogle Scholar
  34. Feringa ER, Johnson RD, Wendt JS (1975) Spinal cord regeneration in rats after immu-nosuppressive treatment. Arch Neurol 32: 676–683PubMedCrossRefGoogle Scholar
  35. Feringa ER, Kinning WK, Britten AG, Vahlsing HL (1976) Recovery in rats after spinal cord injury. Neurology 26: 839–843PubMedCrossRefGoogle Scholar
  36. Feringa EF, Nelson KR, Vahlsing HL, Dauser RC (1979) Spinal cord regeneration in rats made immunologically unresponsive to CNS antigens. J Neurol Neurosurg Psychiatry 42: 642–648PubMedCrossRefGoogle Scholar
  37. Fernandez E, Pallini R, Lauretti L. Mercanti D, Serra A, Calissano P (1993) Spinal cord transection in adult rats: effect of local infusion of nerve growth factor on the corticospinal tract axons. Neurosurgery 33: 889–893PubMedCrossRefGoogle Scholar
  38. Filoni S (1981) La rigenerazione nei Vertebrati. Quad Morfol Funz Comp, Piccin, PadovaGoogle Scholar
  39. Gannuschkina IV, Johansson BB, Person LI (1982) Increased blood brain barrier dysfunction around cerebral slab wounds in rat immunized to brain antigens. Acta Neurol Scand 66:482–487CrossRefGoogle Scholar
  40. Gelderd JB, Matthews MA, StOnge ME Faciane CL (1980) Qualitative and quantitative effects of ACHT, Pyromen, Cytoxan and isobutyl-2-cyanoacrylate treatment following spinal cord transection in rats, Acta Neurobioi Exp 40: 439–500Google Scholar
  41. Gerard RW, Koppany T (1962) Studies on spinal cord regeneration in rat. Arn J Physiol 76: 211–212Google Scholar
  42. Gilden D, Delvin M, Wromblewska L (1978) A technique for the elution of cell-surface antibody from human brain tissue. Ann Neurol 3: 403–405PubMedCrossRefGoogle Scholar
  43. Giulian D, Robertson C (1990) Inhibition of mononuclear phagocytes reduces ischemic injury in the spinal cord. Ann Neurol 27: 33–42PubMedCrossRefGoogle Scholar
  44. Guth L, Albuquerque EX, Deshpande SS, Barret CP, Donati EJ, Warnick JE (1980) Ineffectiveness of enzyme therapy on regeneration in the transected spinal cord of the rat. J Neurosurg 52: 73–86PubMedCrossRefGoogle Scholar
  45. Guth L, Barret CP, Donati EJ, Deshapande SS, Albuquerque EX (1981) Histopathological reactions and axonal regeneration in the transected spinal cord of hibernating squirrel. J Comp Neurol 203: 297–308PubMedCrossRefGoogle Scholar
  46. Hockfieid S (1987) A mab to unique cerebellar neuron generated by immunosuppression and rapid immunisation. Science 237: 67–70CrossRefGoogle Scholar
  47. Hofstetter W, Heusser CH, Blaser K (1985) Nonspecific binding of mouse IgM antibodies to lipid antigen. J Neuroimmunol 7: 207–214PubMedCrossRefGoogle Scholar
  48. Iwashita Y, Kawaguchi S, Murata M (1994) Restoration of function by replacement of spinal cord segments in the rat. Nature (Lond) 367: 167–169PubMedCrossRefGoogle Scholar
  49. Kajihara K. Kawanaga HM, DelaTorre JC, Mullan S (1973) Dimethylsulfoxyde in the treatment of experimental acute spinal cord injury. Surg Neurol 1: 16–22PubMedGoogle Scholar
  50. Kaideron N, Alfieri AA, Fuka Z (1990) Beneficial effects of x-irradiation on recovery of lesioned mammalian central nervous system. Proc Nati Acad Sei USA 87: 10058–10062CrossRefGoogle Scholar
  51. Kalil K, Reh TH (1982) A light and electron microscopic study of the regrowing pyramidal tract fibres. J Comp Neurol 211: 265–275PubMedCrossRefGoogle Scholar
  52. Kelly TA (1988) The role of the immune system in central nervous system regeneration (theoretical considerations). Med Hypoth 26: 13–15CrossRefGoogle Scholar
  53. Kiernan JA (1979) Hypothesis concerned with axonal regeneration in the mammalian nervous system. Biol Rev 54: 155–197PubMedCrossRefGoogle Scholar
  54. Kunkel-Bagden E, Dai HN, Bregman BS (1993) Method to asses the development and recovery of locomotor function after spinal cord injury in rats. Exp Neurol 119: 153–164PubMedCrossRefGoogle Scholar
  55. Lauro G, Margotta V, Venturini G, Teichner A, Caronti B, Palladini G (1992) Correlations between immune response and CNS regeneration in vertebrate phylogenesis. Boll Zool 59: 215–220CrossRefGoogle Scholar
  56. Littrel JL (1955) Apparent functional restitution in pyromen treated spinal cord. In: Windle WF (ed) Regeneration in CNS. Thomas, Springfield, pp 219–228Google Scholar
  57. Marchalonis JJ (1977) Immunity in Evolution. Arnold, London.Google Scholar
  58. Margotta V, Filoni S, Venturini G, Lauro GM, Scorsini D, Palladini G (1989 a) Auto-immunity and central nervous system regeneration in Urodele Amphibians. J Hirnforsch 30: 99–106PubMedGoogle Scholar
  59. Margotta V, Lauro GM, Di Lorenzo N, Grossi M, Scorsini D, Grifone N, Palladini G (1989b) Central axonal regeneration and autoimmunity in adult birds. J Hirnforsch 5: 595–602Google Scholar
  60. Martin GF, Xiao Ming X (1988) Evidence of developmental plasticity of the neurospinal tract. Studies using the North American opossum. Develop Brain Res 39: 308–309CrossRefGoogle Scholar
  61. Marx L (1980) Regeneration in central nervous system. Science 209: 379–380Google Scholar
  62. Masada S (1965) Immunological studies of brain injuries. Clin Neurol 5: 547–555Google Scholar
  63. Matinian LA, Andreasian AS (1973) [Enzyme therapy in organic lesions of the spinal cord] Akademia Nauk Armenian SSR, 1973, pp 94Google Scholar
  64. [englisch transi.: Los Angeles: Brain Information Service, University of California, 1976, pp 156]Google Scholar
  65. Mizrachi J, Ohry I (1983) Systemic humoral factors partecipating in the course of spinal cord injuries. Paraplegia 21: 287–293PubMedCrossRefGoogle Scholar
  66. Muhl H, Kunz D, Rob P, Pfeilschiter J (1993) Cyclosporin derivatives inhibit interleukin 1 (induction of nitric oxide synthase in renal mesangial cells. Eur J Pharmacol 249: 95–100PubMedCrossRefGoogle Scholar
  67. Nona SN (1995) Regenerative failure in the mammalian CNS. TINS 18: 128PubMedGoogle Scholar
  68. Owens T, Renno T, Taupin V, Krakowski M (1994) Inflammatory cytokines in the brain: does the CNS shape immune response? Immunol Today 15: 566–571PubMedCrossRefGoogle Scholar
  69. Palladini G, Alfei L (1965) Observations concerning the regeneration of the spinal cord of the adult rat during treatment with antiblastic substances, In: Kiortsis V, Trapusch HAL (eds) Regeneration in Animals and Related Problems. North-Holland, Amsterdam, pp 515–520Google Scholar
  70. Palladini G, Lauro GM (1988) Neuroimmunologia: stato attuale delle conoscenze. Quaderni di Neuropatologia 3: 19–30Google Scholar
  71. Palladini G, Papalia C (1970) La barriera ematoencefalica per il ferrocianuro nella ontogenesi del pollo. Acta Neurol 25: 137–140Google Scholar
  72. Palladini G, Grossi M, Maleci A, Lauro GM, Guidetti B (1987) Immunocomplexes in rat and rabbit spinal cord after injury. Exp Neurol 95: 639–651PubMedCrossRefGoogle Scholar
  73. Palladini G, Caronti B, Pozzessere G, Teichner A, Buttarelli FR, Morselli E, Valle E, Venturini, Fortuna A, Pontieri FE (1996) Treatment with Cyclosporine A promotes axonal regeneration in rats submitted to transverse section of the spinal cord-II-Recovery of function. J Hirnforsch 37: 145–153PubMedGoogle Scholar
  74. Palladini G, Caronti B, Buttarelli FR, Teichner A, Morselli E, Maione D, Venturini G, Pontieri FE (1998) Involvement of the immune system in the abortive regeneration in mammalia central nervous system. Int J Neurol (in pressGoogle Scholar
  75. Pettgrew RK (1980) Evaluation of the use of enzymes for functional restitution after spinal cord severance in rat. Exp Neurol 68: 284–294CrossRefGoogle Scholar
  76. Pozzessere G, Valle E, Santoro A, Delfini R, Rino PA, Cantore G, Morocutti C (1987) Prognostic value of early somatosensory evoked potentials during carotid surgery: relationship with electroencephalogram, stump pressure and clinical outcome. Acta Neurochir (Wien) 89: 28–33CrossRefGoogle Scholar
  77. Prochazka, Voltherova M, Stephan J (1971) Studies on immunological reaction after brain injuries. II. Int J Surg 55: 322–326Google Scholar
  78. Raffaelli E, Palladini G (1969) Rigenerazione delle cellule e degli assoni del midollo spinale dorsale di Lacerta sicula. Boll Zool 36: 105–310CrossRefGoogle Scholar
  79. Ramon y Cajal S (1907) Notes sur la dégénérescence traumatique des fibres du cervelet et du cerveau, fr Lab Rech Biol (Madrid) 5: 305–115Google Scholar
  80. Ramon y Cajal S (1928) Degeneration and Regeneration of Nervous System. University Press, LondonGoogle Scholar
  81. Reh T, Kalil K (1982) Functional role of regrowing pyramidal tract fibres. J Comp Neurol 211: 276–283PubMedCrossRefGoogle Scholar
  82. Reier DJ, Holle JD (1988) The glial scar: its bearing axonal elongation and transplantation approaches to CNS. In: Watzan SG (ed) Advances in Neurology: Functional Recovery in Neurological Disease. Raven Press, New York, pp 87–138Google Scholar
  83. Rutka JT, Apodaca G, Stern R, Rosemhlum M (1988) The extracellular matrix in the central and peripheral nervous system: structure and function. J Neurosurg 69: 155–170PubMedCrossRefGoogle Scholar
  84. Schnell L, Schwab ME (1990) Axonal regeneration in the rat spinal cord produced by an antibody against myelin-associated neurite growth inhibitors. Nature (Lond) 343: 269–272CrossRefGoogle Scholar
  85. Schnell L, Schneider R, Kolbeck R, Sardo YA, Schwab ME (1994) Neurotrophine-3 enhances sprouting of corticospinal tract during development and after adult spinal cord lesion. Nature (Lond) 367: 170–173CrossRefGoogle Scholar
  86. Schreiber SL, Crabtree GR (1992) The mechanism of action of cyclosporine A and FK506. Immunol Today 13: 336–139CrossRefGoogle Scholar
  87. Schwab ME, Caroni P (1988) Oligodendrocytes and CNS myelin are nonpermissive substrate for neurite growth and fibroblast spreading in vitro. J Neurosci 8: 2381–2393PubMedGoogle Scholar
  88. Sharma HS, Lindholm D, Alm R Gordh T, Olsson Y, Westman J (1996) Topical application of brain-derived neurotrophic factor nitric oxide synthase following focal trauma to the rat spinal cord. XVI International Winter Meeting, Swiss Society of Neuropathology. Degeneration and Regeneration in the Nervous System. Abstract Booklet, p 16Google Scholar
  89. Sivron T, Schwartz M (1995) Glial cell types, lineages and response to injury in rat and fish: implication for regeneration. Glia 13: 157–165PubMedCrossRefGoogle Scholar
  90. So F, Aguayo AJ (1985) Lenghty regrowlh of cut axons from ganglion cells after peripheral nerve transplantation into the retina of adult rat. Brain Res 328: 349–354PubMedCrossRefGoogle Scholar
  91. Stefan J, Prochazka M, Volterova M (1971) Studies of immunological reactions after brain injury. L Antibodies against brain tissue lipids after experimental injury of the brain in rabbits. Int Surgery 55: 316–321Google Scholar
  92. Stichel CC. Muller HW (1995) Regenerative failure in the mammalian CNS. TiNS 18, p 128PubMedGoogle Scholar
  93. Stitz L (1992) Induction of antigen-specific tolerance by ciclosporine A. Eur J Immunol 22: 1995–2001PubMedCrossRefGoogle Scholar
  94. Stuart EG (1955) Time reaction and possible mechanism of pyromen and desoxycorticos-terone acetate in CNS regeneration. In: Windle FW (ed) Regeneration in CNS. Thomas, Springfield, pp 162–170Google Scholar
  95. Teichner A, Morselli E, Buttarelli FR, Caronti B, Pontieri FE, Venturini G, Palladini (1993) Treatment with cyclosporine A promotes axonal regeneration in rats submitted to transverse section of the spinal cord. J Hirnforsch 34: 343–349PubMedGoogle Scholar
  96. Willard M, Simon C (1981) Antibody decoration of neurofilaments. J Cell Biol 89: 198–205PubMedCrossRefGoogle Scholar
  97. Willenborg DO, Staten EA, Eidelberg E (1977) Studies on cell-mediated hypersensitivity to neural antigens after experimental spinal cord injury. Exp Neurol 54: 383–392PubMedCrossRefGoogle Scholar
  98. Wu W, Scott DE (1993) Increased expression of nitric oxyde synthase in hypothalamic neuronal regeneration. Exp Neurol 12 j: 279–283Google Scholar
  99. Wu W, Liuzzi FJ, Schinco FR Depto AS, Li Y, Mong JA, Dawson TM, Snyder SH (1994) Neuronal nitric oxide synthase is induced in spinal neurons by traumatic injury. Neuroscience 61: 719–726PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Wien 1998

Authors and Affiliations

  • G. Palladini
    • 1
  • B. Caronti
    • 1
  1. 1.Dipartimento di Scienze NeurologicheUniversità ‘La Sapienza’RomaItaly

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