Regeneration Failure in the CNS

Cellular and Molecular Mechanisms
  • Anne D. Zurn
  • Christine E. Bandtlow
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 557)


Spinal Cord Spinal Cord Injury Axonal Regeneration Glial Scar Chondroitin Sulfate Proteoglycan 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Bareyre FM, Schwab ME. Inflammation, degeneration and regeneration in the injured spinal cord: insights from DNA microarrays. Trends Neurosci 2003; 26:555–63.PubMedGoogle Scholar
  2. 2.
    De Winter F, Holtmaat AJ, Verhaagen J. Neuropilin and class 3 semaphorins in nervous system regeneration. Adv Exp Med Biol 2002; 515:115–39.PubMedGoogle Scholar
  3. 3.
    Filbin MT. Myelin-associated inhibitors of axonal regeneration in the adult mammalian CNS. Nat Rev Neurosci 2003; 4:703–13.PubMedGoogle Scholar
  4. 4.
    Huber AB, Schwab ME. Nogo-A, a potent inhibitor of neurite outgrowth and regeneration. Biol Chem 2000; 381:407–19.PubMedGoogle Scholar
  5. 5.
    Hunt D, Coffin RS, Anderson PN. The Nogo receptor, its ligands and axonal regeneration in the spinal cord; a review. J Neurocytol 2002; 31:93–120.PubMedGoogle Scholar
  6. 6.
    Morgenstern DA., Asher RA, Fawcett JW. Chondroitin sulphate proteoglycans in the CNS injury response. Prog Brain Res 2002; 137:313–32.PubMedGoogle Scholar
  7. 7.
    Goldberg JL, Barres BA. The relationship between neuronal survival and regeneration. Annu Rev Neurosci 2000; 23:579–612.PubMedGoogle Scholar
  8. 8.
    Sofroniew MV, Isacson O. Distribution of degeneration of cholinergic neurons in the septum following axotomy in different portions of the fimbria-fornix: a correlation between degree of cell loss and proximity of neuronal somata to the lesion. J Chem Neuroanat 1988; 1:327–37.PubMedGoogle Scholar
  9. 9.
    Stoll G, Jander S, Myers RR. Degeneration and regeneration of the peripheral nervous system: from Augustus Waller’s observations to neuroinflammation. J Peripher Nerv Syst 2002; 7:13–27.PubMedGoogle Scholar
  10. 10.
    Chen DF, Jhaveri S, Schneider GE. Intrinsic changes in developing retinal neurons result in regenerative failure of their axons. Proc Natl Acad Sci USA 1995; 92:7287–91.PubMedGoogle Scholar
  11. 11.
    Dusart I, Airaksinen MS, Sotelo C. Purkinje cell survival and axonal regeneration are age dependent: an in vitro study. J Neurosci 1997; 17:3710–26.PubMedGoogle Scholar
  12. 12.
    Gianola S, Rossi F. Evolution of the Purkinje cell response to injury and regenerative potential during postnatal development of the rat cerebellum. J Comp Neurol 2001; 430:101–17.PubMedGoogle Scholar
  13. 13.
    Steeves JD, Keirstead HS, Ethell DW et al. Permissive and restrictive periods for brainstem-spinal regeneration in the chick. Prog Brain Res 1994; 103:243–62.PubMedGoogle Scholar
  14. 14.
    Bates CA, Stelzner DJ. Extension and regeneration of corticospinal axons after early spinal injury and the maintenance of corticospinal topography. Exp Neurol 1993; 123:106–17.PubMedGoogle Scholar
  15. 15.
    Firkins SS, Bates CA, Stelzner DJ. Corticospinal tract plasticity and astroglial reactivity after cervical spinal injury in the postnatal rat. Exp Neurol 1993; 120:1–15.PubMedGoogle Scholar
  16. 16.
    Hasan SJ, Keirstead HS, Muir GD et al. Axonal regeneration contributes to repair of injured brainstem-spinal neurons in embryonic chick. J Neurosci 1993; 13:492–507.PubMedGoogle Scholar
  17. 17.
    Keirstead HS, Hasan SJ, Muir GD et al. Suppression of the onset of myelination extends the permissive period for the functional repair of embryonic spinal cord. Proc Natl Acad Sci USA 1992; 89:11664–8.PubMedGoogle Scholar
  18. 18.
    Bouslama-Oueghlani L, Wehrle R, Sotelo C et al. The developmental loss of the ability of Purkinje cells to regenerate their axons occurs in the absence of myelin: an in vitro model to prevent myelination. J Neurosci 2003; 23:8318–29.PubMedGoogle Scholar
  19. 19.
    Goldberg JL, Klassen MP, Hua Y et al. Amacrine-signaled loss of intrinsic axon growth ability by retinal ganglion cells. Science 2002; 296:1860–4.PubMedGoogle Scholar
  20. 20.
    Mori N, Morii H. SCG10-related neuronal growth-associated proteins in neural development, plasticity, degeneration, and aging. J Neurosci Res 2002; 70:264–73.PubMedGoogle Scholar
  21. 21.
    Cai D, Qiu J, Cao Z et al. Neuronal cyclic AMP controls the developmental loss in ability of axons to regenerate. J Neurosci 2001; 21:4731–9.PubMedGoogle Scholar
  22. 22.
    Bandtlow CE, Loschinger J. Developmental changes in neuronal responsiveness to the CNS myelin-associated neurite growth inhibitor NI-35/250. Eur J Neurosci 1997; 9:2743–52.PubMedGoogle Scholar
  23. 23.
    Goldberg JL, Espinosa JS, Xu Y et al. Retinal ganglion cells do not extend axons by default: promotion by neurotrophic signaling and electrical activity. Neuron 2002; 33:689–702.PubMedGoogle Scholar
  24. 24.
    Chen DF, Schneider GE, Martinou JC et al. Bcl-2 promotes regeneration of severed axons in mammalian CNS. Nature 1997; 385:434–9.PubMedGoogle Scholar
  25. 25.
    Fernandes K. Gene expression in axotomized neurons: identifying the intrinsic determinants of axonal growth. In: Ingoglia NA, ed. Axonal regeneration in the central nervous system. New York: Marcel Dekker Inc., 2000:219–266.Google Scholar
  26. 26.
    Broude E, McAtee M, Kelley MS et al. c-Jun expression in adult rat dorsal root ganglion neurons: differential response after central or peripheral axotomy. Exp Neurol 1997; 148:367–77.PubMedGoogle Scholar
  27. 27.
    Chong MS, Reynolds ML, Irwin N et al. GAP-43 expression in primary sensory neurons following central axotomy. J Neurosci 1994; 14:4375–84.PubMedGoogle Scholar
  28. 28.
    Schreyer DJ, Skene JH. Injury-associated induction of GAP-43 expression displays axon branch specificity in rat dorsal root ganglion neurons. J Neurobiol 1993; 24:959–70.PubMedGoogle Scholar
  29. 29.
    Schwaiger FW, Hager G, Schmitt AB et al. Peripheral but not central axotomy induces changes in Janus kinases (JAK) and signal transducers and activators of transcription (STAT). Eur J Neurosci 2000; 12:1165–76.PubMedGoogle Scholar
  30. 30.
    Aigner L, Arber S, Kapfhammer JP et al. Overexpression of the neural growth-associated protein GAP-43 induces nerve sprouting in the adult nervous system of transgenic mice. Cell 1995; 83:269–78.PubMedGoogle Scholar
  31. 31.
    Buffo A, Holtmaat AJ, Savio T et al. Targeted overexpression of the neurite growth-associated protein B-50/GAP-43 in cerebellar Purkinje cells induces sprouting after axotomy but not axon regeneration into growth-permissive transplants. J Neurosci 1997; 17:8778–91.PubMedGoogle Scholar
  32. 32.
    Mason MR, Campbell G, Caroni P et al. Overexpression of GAP-43 in thalamic projection neurons of transgenic mice does not enable them to regenerate axons through peripheral nerve grafts. Exp Neurol 2000; 165:143–52.PubMedGoogle Scholar
  33. 33.
    Bomze HM, Bulsara KR, Iskandar BJ et al. Spinal axon regeneration evoked by replacing two growth cone proteins in adult neurons. Nat Neurosci 2001; 4:38–43.PubMedGoogle Scholar
  34. 34.
    Bonilla IE, Tanabe K, Strittmatter SM. Small proline-rich repeat protein 1A is expressed by axotomized neurons and promotes axonal outgrowth. J Neurosci 2002; 22:1303–15.PubMedGoogle Scholar
  35. 35.
    Tanabe K, Bonilla I, Winkles JA et al. Fibroblast growth factor-inducible-14 is induced in axotomized neurons and promotes neurite outgrowth. J Neurosci 2003; 23:9675–86.PubMedGoogle Scholar
  36. 36.
    Hull M, Bahr M. Differential regulation of c-JUN expression in rat retinal ganglion cells after proximal and distal optic nerve transection. Neurosci Lett 1994; 178:39–42.PubMedGoogle Scholar
  37. 37.
    Fernandes KJ, Fan DP, Tsui BJ et al. Influence of the axotomy to cell body distance in rat rubrospinal and spinal motoneurons: differential regulation of GAP-43, tubulins, and neurofilament-M. J Comp Neurol 1999; 414:495–510.PubMedGoogle Scholar
  38. 38.
    Mason MR, Lieberman AR, Anderson PN. Corticospinal neurons up-regulate a range of growth-associated genes following intracortical, but not spinal, axotomy. Eur J Neurosci 2003; 18:789–802.PubMedGoogle Scholar
  39. 39.
    Richardson PM, McGuinness UM, Aguayo AJ. Axons from CNS neurons regenerate into PNS grafts. Nature 1980; 284:264–5.PubMedGoogle Scholar
  40. 40.
    Chong MS, Reynolds ML, Irwin N et al. GAP-43 expression in primary sensory neurons following central axotomy. J Neurosci 1994; 14:4375–84.PubMedGoogle Scholar
  41. 41.
    Mason MR, Lieberman AR, Grenningloh G et al. Transcriptional upregulation of SCG10 and CAP-23 is correlated with regeneration of the axons of peripheral and central neurons in vivo. Mol Cell Neurosci 2002; 20:595–615.PubMedGoogle Scholar
  42. 42.
    Neumann S, Woolf CJ. Regeneration of dorsal column fibers into and beyond the lesion site following adult spinal cord injury. Neuron 1999; 23:83–91.PubMedGoogle Scholar
  43. 43.
    Pasterkamp RJ, Verhaagen J. Emerging roles for semaphorins in neural regeneration. Brain Res Brain Res Rev 2001; 35:36–54.PubMedGoogle Scholar
  44. 44.
    Rossi F, Strata P. Reciprocal trophic interactions in the adult climbing fibre-Purkinje cell system. Prog Neurobiol 1995; 47:341–69.PubMedGoogle Scholar
  45. 45.
    Inman DM, Steward O. Ascending sensory, but not other long-tract axons, regenerate into the connective tissue matrix that forms at the site of a spinal cord injury in mice. J Comp Neurol 2003; 462:431–49.PubMedGoogle Scholar
  46. 46.
    David S, Aguayo AJ. Axonal elongation into peripheral nervous system “bridges” after central nervous system injury in adult rats. Science 1981; 214:931–3.PubMedGoogle Scholar
  47. 47.
    Pettigrew DB, Crutcher KA. White matter of the CNS supports or inhibits neurite outgrowth in vitro depending on geometry. J Neurosci 1999; 19:8358–66.PubMedGoogle Scholar
  48. 48.
    Schwab ME, Bartholdi D. Degeneration and regeneration of axons in the lesioned spinal cord. Physiol Rev 1996; 76:319–70.PubMedGoogle Scholar
  49. 49.
    Faulkner JR, Herrmann JE, Woo MJ et al. Reactive astrocytes protect tissue and preserve function after spinal cord injury. J Neurosci 2004; 24:2143–55.PubMedGoogle Scholar
  50. 50.
    Cui W, Allen ND, Skynner M et al. Inducible ablation of astrocytes shows that these cells are required for neuronal survival in the adult brain. Glia 2001; 34:272–82.PubMedGoogle Scholar
  51. 51.
    Constam DB, Philipp J, Malipiero UV et al. Differential expression of transforming growth factor-beta 1,-beta 2, and-beta 3 by glioblastoma cells, astrocytes, and microglia. J Immunol 1992; 148:1404–10.PubMedGoogle Scholar
  52. 52.
    Muller HW, Junghans U, Kappler J. Astroglial neurotrophic and neurite-promoting factors. Pharmacol Ther 1995; 65:1–18.PubMedGoogle Scholar
  53. 53.
    Hoke A, Silver J. Proteoglycans and other repulsive molecules in glial boundaries during development and regeneration of the nervous system. Prog Brain Res 1996; 108:149–63.PubMedGoogle Scholar
  54. 54.
    Kreutzberg GW. Microglia: a sensor for pathological events in the CNS. Trends Neurosci 1996; 19:312–8.PubMedGoogle Scholar
  55. 55.
    Raivich G, Jones LL, Werner A et al. Molecular signals for glial activation: pro-and anti-inflammatory cytokines in the injured brain. Acta Neurochir Suppl 1999; 73:21–30.PubMedGoogle Scholar
  56. 56.
    McTigue DM, Wei P, Stokes BT. Proliferation of NG2-positive cells and altered oligodendrocyte numbers in the contused rat spinal cord. J Neurosci 2001; 21:3392–400.PubMedGoogle Scholar
  57. 57.
    Levine JM, Reynolds R, Fawcett JW. The oligodendrocyte precursor cell in health and disease. Trends Neurosci 2001; 24:39–47.PubMedGoogle Scholar
  58. 58.
    Carbonell AL, Boya J. Ultrastructural study on meningeal regeneration and meningo-glial relationships after cerebral stab wound in the adult rat. Brain Res 1988; 439:337–44.PubMedGoogle Scholar
  59. 59.
    Shearer MC, Fawcett JW. The astrocyte/meningeal cell interface—a barrier to successful nerve regeneration? Cell Tissue Res 2001; 305:267–73.PubMedGoogle Scholar
  60. 60.
    Coleman MP, Perry VH. Axon pathology in neurological disease: a neglected therapeutic target. Trends Neurosci 2002; 25:532–7.PubMedGoogle Scholar
  61. 61.
    Shamash S, Reichert F, Rotshenker S. The cytokine network of Wallerian degeneration: tumor necrosis factor-alpha, interleukin-1alpha, and interleukin-1beta. J Neurosci 2002; 22:3052–60.PubMedGoogle Scholar
  62. 62.
    Stoll G, Jander S. The role of microglia and macrophages in the pathophysiology of the CNS. Prog Neurobiol 1999; 58:233–47.PubMedGoogle Scholar
  63. 63.
    George R, Griffin JW. Delayed macrophage responses and myelin clearance during Wallerian degeneration in the central nervous system: the dorsal radiculotomy model. Exp Neurol 1994; 129:225–36.PubMedGoogle Scholar
  64. 64.
    Bandtlow C, Zachleder T, Schwab ME. Oligodendrocytes arrest neurite growth by contact inhibition. J Neurosci 1990; 10:3837–48.PubMedGoogle Scholar
  65. 65.
    Caroni P, Savio T, Schwab ME. Central nervous system regeneration: oligodendrocytes and myelin as non-permissive substrates for neurite growth. Prog Brain Res 1988; 78:363–70.PubMedGoogle Scholar
  66. 66.
    Beattie MS, Hermann GE, Rogers RC et al. Cell death in models of spinal cord injury. Prog Brain Res 2002; 137:37–47.PubMedGoogle Scholar
  67. 67.
    Allan SM, Rothwell NJ. Cytokines and acute neurodegeneration. Nat Rev Neurosci 2001; 2:734–44.PubMedGoogle Scholar
  68. 68.
    Frei E, Klusman I, Schnell L et al. Reactions of oligodendrocytes to spinal cord injury: cell survival and myelin repair. Exp Neurol 2000; 163:373–80.PubMedGoogle Scholar
  69. 69.
    Dong H, Fazzaro A, Xiang C et al. Enhanced oligodendrocyte survival after spinal cord injury in Bax-deficient mice and mice with delayed Wallerian degeneration. J Neurosci 2003; 23:8682–91.PubMedGoogle Scholar
  70. 70.
    Casha S, Yu WR, Fehlings MG. Oligodendroglial apoptosis occurs along degenerating axons and is associated with FAS and p75 expression following spinal cord injury in the rat. Neuroscience 2001; 103:203–18.PubMedGoogle Scholar
  71. 71.
    Grossman SD, Rosenberg LJ, Wrathall JR. Temporal-spatial pattern of acute neuronal and glial loss after spinal cord contusion. Exp Neurol 2001; 168:273–82.PubMedGoogle Scholar
  72. 72.
    Kimelberg HK. Astrocytic edema in CNS trauma. J Neurotrauma 1992; 9Suppl 1, S71–81.PubMedGoogle Scholar
  73. 73.
    Bullock R, Maxwell WL, Graham DI et al. Glial swelling following human cerebral contusion: an ultrastructural study. J Neurol Neurosurg Psychiatry 1991; 54:427–34.PubMedGoogle Scholar
  74. 74.
    Wyss-Coray T, Mucke L. Inflammation in neurodegenerative disease—a double-edged sword. Neuron 2002; 35:419–32.PubMedGoogle Scholar
  75. 75.
    Schwartz M, Lazarov-Spiegler O, Rapalino O et al. Potential repair of rat spinal cord injuries using stimulated homologous macrophages. Neurosurgery 1999; 44:1041–5; discussion 1045–6.PubMedGoogle Scholar
  76. 76.
    Rostworowski M, Balasingam V, Chabot S et al. Astrogliosis in the neonatal and adult murine brain post-trauma: elevation of inflammatory cytokines and the lack of requirement for endogenous interferon-gamma. J Neurosci 1997; 17:3664–74.PubMedGoogle Scholar
  77. 77.
    Yong VW, Moumdjian R, Yong FP et al. Gamma-interferon promotes proliferation of adult human astrocytes in vitro and reactive gliosis in the adult mouse brain in vivo. Proc Natl Acad Sci USA 1991; 88:7016–20.PubMedGoogle Scholar
  78. 78.
    Logan A, Berry M, Gonzalez AM et al. Effects of transforming growth factor beta 1 on scar production in the injured central nervous system of the rat. Eur J Neurosci 1994; 6:355–63.PubMedGoogle Scholar
  79. 79.
    Lagord C, Berry M, Logan A. Expression of TGFbeta2 but not TGFbeta1 correlates with the deposition of scar tissue in the lesioned spinal cord. Mol Cell Neurosci 2002; 20:69–92.PubMedGoogle Scholar
  80. 80.
    Giulian D, Lachman LB. Interleukin-1 stimulation of astroglial proliferation after brain injury. Science 1985; 228:497–9.PubMedGoogle Scholar
  81. 81.
    Asher RA, Morgenstern DA, Fidler PS et al. Neurocan is upregulated in injured brain and in cytokine-treated astrocytes. J Neurosci 2000; 20:2427–38.PubMedGoogle Scholar
  82. 82.
    Smith GM, Hale JH. Macrophage/Microglia regulation of astrocytic tenascin: synergistic action of transforming growth factor-beta and basic fibroblast growth factor. J Neurosci 1997; 17:9624–33.PubMedGoogle Scholar
  83. 83.
    Sroga JM, Jones TB, Kigerl KA et al. Rats and mice exhibit distinct inflammatory reactions after spinal cord injury. J Comp Neurol 2003; 462:223–40.PubMedGoogle Scholar
  84. 84.
    Inman D, Guth L, Steward O. Genetic influences on secondary degeneration and wound healing following spinal cord injury in various strains of mice. J Comp Neurol 2002; 451:225–35.PubMedGoogle Scholar
  85. 85.
    Steward O, Schauwecker PE, Guth L et al. Genetic approaches to neurotrauma research: opportunities and potential pitfalls of murine models. Exp Neurol 1999; 157:19–42.PubMedGoogle Scholar
  86. 86.
    Caroni P, Schwab ME. Two membrane protein fractions from rat central myelin with inhibitory properties for neurite growth and fibroblast spreading. J Cell Biol 1988; 106:1281–8.PubMedGoogle Scholar
  87. 87.
    Schnell L, Schwab ME. Axonal regeneration in the rat spinal cord produced by an antibody against myelin-associated neurite growth inhibitors. Nature 1990; 343:269–72.PubMedGoogle Scholar
  88. 88.
    Sicotte M, Tsatas O, Jeong SY et al. Immunization with myelin or recombinant Nogo-66/MAG in alum promotes axon regeneration and sprouting after corticospinal tract lesions in the spinal cord. Mol Cell Neurosci 2003; 23:251–63.PubMedGoogle Scholar
  89. 89.
    Huang DW, McKerracher L, Braun PE et al. A therapeutic vaccine approach to stimulate axon regeneration in the adult mammalian spinal cord. Neuron 1999; 24:639–47.PubMedGoogle Scholar
  90. 90.
    Bregman BS, Kunkel-Bagden E, Schnell L et al. Recovery from spinal cord injury mediated by antibodies to neurite growth inhibitors. Nature 1995; 378:498–501.PubMedGoogle Scholar
  91. 91.
    GrandPre T, Li S, Strittmatter SM. Nogo-66 receptor antagonist peptide promotes axonal regeneration. Nature 2002; 417:547–51.PubMedGoogle Scholar
  92. 92.
    Grados-Munro EM, Fournier AE. Myelin-associated inhibitors of axon regeneration. J Neurosci Res 2003; 74:479–85.PubMedGoogle Scholar
  93. 93.
    Salzer JL, Holmes WP, Colman DR. The amino acid sequences of the myelin-associated glycoproteins: homology to the immunoglobulin gene superfamily. J Cell Biol 1987; 104:957–65.PubMedGoogle Scholar
  94. 94.
    Willison HJ, Ilyas AI, O’Shannessy DJ et al. Myelin-associated glycoprotein and related glycoconjugates in developing cat peripheral nerve: a correlative biochemical and morphometric study. J Neurochem 1987; 49:1853–62.PubMedGoogle Scholar
  95. 95.
    Johnson PW, Abramow-Newerly W, Seilheimer B et al. Recombinant myelin-associated glycoprotein confers neural adhesion and neurite outgrowth function. Neuron 1989; 3:377–85.PubMedGoogle Scholar
  96. 96.
    Turnley AM, Bartlett PF. MAG and MOG enhance neurite outgrowth of embryonic mouse spinal cord neurons. Neuroreport 1998; 9:1987–90.PubMedGoogle Scholar
  97. 97.
    Mukhopadhyay G, Doherty P, Walsh FS et al. A novel role for myelin-associated glycoprotein as an inhibitor of axonal regeneration. Neuron 1994; 13:757–67.PubMedGoogle Scholar
  98. 98.
    Neumann S, Bradke F, Tessier-Lavigne M et al. Regeneration of sensory axons within the injured spinal cord induced by intraganglionic cAMP elevation. Neuron 2002; 34:885–93.PubMedGoogle Scholar
  99. 99.
    Qiu J, Cai D, Filbin MT. A role for cAMP in regeneration during development and after injury. Prog Brain Res 2002; 137:381–7.PubMedGoogle Scholar
  100. 100.
    Hirata K, Kawabuchi M. Myelin phagocytosis by macrophages and nonmacrophages during Wallerian degeneration. Microsc Res Tech 2002; 57:541–7.PubMedGoogle Scholar
  101. 101.
    Schafer M, Fruttiger M, Montag D et al. Disruption of the gene for the myelin-associated glycoprotein improves axonal regrowth along myelin in C57BL/Wlds mice. Neuron 1996; 16:1107–13.PubMedGoogle Scholar
  102. 102.
    Li M, Shibata A, Li C et al. Myelin-associated glycoprotein inhibits neurite/axon growth and causes growth cone collapse. J Neurosci Res 1996; 46:404–14.PubMedGoogle Scholar
  103. 103.
    Bartsch U, Bandtlow CE, Schnell L et al. Lack of evidence that myelin-associated glycoprotein is a major inhibitor of axonal regeneration in the CNS. Neuron 1995; 15:1375–81.PubMedGoogle Scholar
  104. 104.
    Prinjha R, Moore SE, Vinson M et al. Inhibitor of neurite outgrowth in humans. Nature 2000; 403:383–4.PubMedGoogle Scholar
  105. 105.
    GrandPre T, Nakamura F, Vartanian T et al. Identification of the Nogo inhibitor of axon regeneration as a Reticulon protein. Nature 2000; 403:439–44.PubMedGoogle Scholar
  106. 106.
    Chen MS, Huber AB, van der Haar ME et al. Nogo-A is a myelin-associated neurite outgrowth inhibitor and an antigen for monoclonal antibody IN-1. Nature 2000; 403:434–9.PubMedGoogle Scholar
  107. 107.
    Spillmann AA, Bandtlow CE, Lottspeich F et al. Identification and characterization of a bovine neurite growth inhibitor (bNI-220). J Biol Chem 1998; 273:19283–93.PubMedGoogle Scholar
  108. 108.
    Oertle T, Schwab ME. Nogo and its paRTNers. Trends Cell Biol 2003; 13:187–94.PubMedGoogle Scholar
  109. 109.
    Oertle T, Klinger M, Stuermer CA et al. A reticular rhapsody: phylogenic evolution and nomenclature of the RTN/Nogo gene family. Faseb J 2003; 17:1238–47.PubMedGoogle Scholar
  110. 110.
    Oertle T, van der Haar ME, Bandtlow CE et al. Nogo-A inhibits neurite outgrowth and cell spreading with three discrete regions. J Neurosci 2003; 23:5393–406.PubMedGoogle Scholar
  111. 111.
    GrandPré T, Nakamura F, Vartanian T et al. Identification of the Nogo inhibitor of axon regeneration as a Reticulon protein. Nature 2000; 403:439–44.PubMedGoogle Scholar
  112. 112.
    Huber AB, Weinmann O, Brosamle C et al. Patterns of Nogo mRNA and protein expression in the developing and adult rat and after CNS lesions. J Neurosci 2002; 22:3553–67.PubMedGoogle Scholar
  113. 113.
    Hunt D, Coffin RS, Prinjha RK et al. Nogo-A expression in the intact and injured nervous system. Mol Cell Neurosci 2003; 24:1083–102.PubMedGoogle Scholar
  114. 114.
    Josephson A, Widenfalk J, Widmer HW et al. NOGO mRNA expression in adult and fetal human and rat nervous tissue and in weight drop injury. Exp Neurol 2001; 169:319–28.PubMedGoogle Scholar
  115. 115.
    Wang X, Chun SJ, Treloar H et al. Localization of Nogo-A and Nogo-66 receptor proteins at sites of axon-myelin and synaptic contact. J Neurosci 2002; 22:5505–15.PubMedGoogle Scholar
  116. 116.
    Schwab ME. Increasing plasticity and functional recovery of the lesioned spinal cord. Prog Brain Res 2002; 137:351–9.PubMedGoogle Scholar
  117. 117.
    Li S, Strittmatter SM. Delayed systemic Nogo-66 receptor antagonist promotes recovery from spinal cord injury. J Neurosci 2003; 23:4219–27.PubMedGoogle Scholar
  118. 118.
    Pot C, Simonen M, Weinmann O et al. Nogo-A expressed in Schwann cells impairs axonal regeneration after peripheral nerve injury. J Cell Biol 2002; 159:29–35.PubMedGoogle Scholar
  119. 119.
    Kim JE, Bonilla IE, Qiu D et al. Nogo-C is sufficient to delay nerve regeneration. Mol Cell Neurosci 2003; 23:451–9.PubMedGoogle Scholar
  120. 120.
    Kim JE, Li S, GrandPre T et al. Axon regeneration in young adult mice lacking Nogo-A/B. Neuron 2003; 38:187–99.PubMedGoogle Scholar
  121. 121.
    Simonen M, Pedersen V, Weinmann O et al. Systemic deletion of the myelin-associated outgrowth inhibitor Nogo-A improves regenerative and plastic responses after spinal cord injury. Neuron 2003; 38:201–11.PubMedGoogle Scholar
  122. 122.
    Zheng B, Ho C, Li S et al. Lack of enhanced spinal regeneration in Nogo-deficient mice. Neuron 2003; 38:213–24.PubMedGoogle Scholar
  123. 123.
    Schnell L, Liebscher T, Weinmann OR et al. Increased regeneration and functional recovery in rats treated with antibodies to NOGO-A and IN NOGO-A knockout mice. In: Program No. 43.11. 2004 Abstract Viewer/Itinerary Planner. Washington, D.S.f.N., 2004. Online, ed.Google Scholar
  124. 124.
    Kottis V, Thibault P, Mikol D et al. Oligodendrocyte-myelin glycoprotein (OMgp) is an inhibitor of neurite outgrowth. J Neurochem 2002; 82:1566–9.PubMedGoogle Scholar
  125. 125.
    Wang KC, Koprivica V, Kim JA et al. Oligodendrocyte-myelin glycoprotein is a Nogo receptor ligand that inhibits neurite outgrowth. Nature 2002; 417:941–4.PubMedGoogle Scholar
  126. 126.
    Mikol DD, Gulcher JR, Stefansson K. The oligodendrocyte-myelin glycoprotein belongs to a distinct family of proteins and contains the HNK-1 carbohydrate. J Cell Biol 1990; 110:471–9.PubMedGoogle Scholar
  127. 127.
    Mikol DD, Stefansson K. A phosphatidylinositol-linked peanut agglutinin-binding glycoprotein in central nervous system myelin and on oligodendrocytes. J Cell Biol 1998; 106:1273–9.Google Scholar
  128. 128.
    Fawcett JW, Asher RA. The glial scar and central nervous system repair. Brain Res Bull 1999; 49:377–91.PubMedGoogle Scholar
  129. 129.
    Fidler PS, Schuette K, Asher RA et al. Comparing astrocytic cell lines that are inhibitory or permissive for axon growth: the major axon-inhibitory proteoglycan is NG2. J Neurosci 1999; 19:8778–88.PubMedGoogle Scholar
  130. 130.
    Logan A, Berry M. Cellular and molecular determinants of glial scar formation. Adv Exp Med Biol 2002; 513:115–58.PubMedGoogle Scholar
  131. 131.
    Muir EM, Adcock KH, Morgenstern DA et al. Matrix metalloproteases and their inhibitors are produced by overlapping populations of activated astrocytes. Brain Res Mol Brain Res 2002; 100:103–17.PubMedGoogle Scholar
  132. 132.
    Properzi F, Asher RA, Fawcett JW. Chondroitin sulphate proteoglycans in the central nervous system: changes and synthesis after injury. Biochem Soc Trans 2003; 31:335–6.PubMedGoogle Scholar
  133. 133.
    Rudge JS, Smith GM, Silver J. An in vitro model of wound healing in the CNS: analysis of cell reaction and interaction at different ages. Exp Neurol 1989; 103:1–16.PubMedGoogle Scholar
  134. 134.
    Silver J, Miller JH. Regeneration beyond the glial scar. Nat Rev Neurosci 2004; 5:146–56.PubMedGoogle Scholar
  135. 135.
    Stichel CC, Niermann H, D’Urso D et al. Basal membrane-depleted scar in lesioned CNS: characteristics and relationships with regenerating axons. Neuroscience 1999; 93:321–33.PubMedGoogle Scholar
  136. 136.
    McKeon RJ, Hoke A, Silver J. Injury-induced proteoglycans inhibit the potential for laminin-mediated axon growth on astrocytic scars. Exp Neurol 1995; 136:32–43.PubMedGoogle Scholar
  137. 137.
    McKeon RJ, Schreiber RC, Rudge JS et al. Reduction of neurite outgrowth in a model of glial scarring following CNS injury is correlated with the expression of inhibitory molecules on reactive astrocytes. J Neurosci 1991; 11:3398–411.PubMedGoogle Scholar
  138. 138.
    Smith-Thomas LC, Fok-Seang J, Stevens J et al. An inhibitor of neurite outgrowth produced by astrocytes. J Cell Sci 1994; 107 (Pt 6):1687–95.PubMedGoogle Scholar
  139. 139.
    Smith-Thomas LC, Stevens J, Fok-Seang J et al. Increased axon regeneration in astrocytes grown in the presence of proteoglycan synthesis inhibitors. J Cell Sci 1995; 108 (Pt 3):1307–15.PubMedGoogle Scholar
  140. 140.
    Hartmann U, Maurer P. Proteoglycans in the nervous system—the quest for functional roles in vivo. Matrix Biol 2001; 20:23–35.PubMedGoogle Scholar
  141. 141.
    Bandtlow CE, Zimmermann DR. Proteoglycans in the developing brain: new conceptual insights for old proteins. Physiol Rev 2000; 80:1267–90.PubMedGoogle Scholar
  142. 142.
    Yamaguchi Y. Lecticans: organizers of the brain extracellular matrix. Cell Mol Life Sci 2000; 57:276–89.PubMedGoogle Scholar
  143. 143.
    Timpl R, Sasaki T, Kostka G et al. Fibulins: a versatile family of extracellular matrix proteins. Nat Rev Mol Cell Biol 2003; 4:479–89.PubMedGoogle Scholar
  144. 144.
    Bekku Y, Su WD, Hirakawa S et al. Molecular cloning of Bral2, a novel brain-specific link protein, and immunohistochemical colocalization with brevican in perineuronal nets. Mol Cell Neurosci 2003; 24:148–59.PubMedGoogle Scholar
  145. 145.
    Oohashi T, Hirakawa S, Bekku Y et al. Bral1, a brain-specific link protein, colocalizing with the versican V2 isoform at the nodes of Ranvier in developing and adult mouse central nervous systems. Mol Cell Neurosci 2002; 19:43–57.PubMedGoogle Scholar
  146. 146.
    Hagihara K, Miura R, Kosaki R et al. Immunohistochemical evidence for the brevican-tenascin-R interaction: colocalization in perineuronal nets suggests a physiological role for the interaction in the adult rat brain. J Comp Neurol 1999; 410:256–64.PubMedGoogle Scholar
  147. 147.
    Seidenbecher CI, Richter K, Rauch U et al. Brevican, a chondroitin sulfate proteoglycan of rat brain, occurs as secreted and cell surface glycosylphosphatidylinositol-anchored isoforms. J Biol Chem 1995; 270:27206–12.PubMedGoogle Scholar
  148. 148.
    Seidenbecher CI, Smalla KH, Fischer N et al. Brevican isoforms associate with neural membranes. J Neurochem 2002; 83:738–46.PubMedGoogle Scholar
  149. 149.
    Yamada H, Fredette B, Shitara K et al. The brain chondroitin sulfate proteoglycan brevican associates with astrocytes ensheathing cerebellar glomeruli and inhibits neurite outgrowth from granule neurons. J Neurosci 1997; 17:7784–95.PubMedGoogle Scholar
  150. 150.
    Schwartz NB, Domowicz M. Proteoglycans in brain development. Glycoconj J 2004; 21:329–41.PubMedGoogle Scholar
  151. 151.
    Ogawa T, Hagihara K, Suzuki M et al. Brevican in the developing hippocampal fimbria: differential expression in myelinating oligodendrocytes and adult astrocytes suggests a dual role for brevican in central nervous system fiber tract development. J Comp Neurol 2001; 432:285–95.PubMedGoogle Scholar
  152. 152.
    Niederost BP, Zimmermann DR, Schwab ME et al. Bovine CNS myelin contains neurite growth-inhibitory activity associated with chondroitin sulfate proteoglycans. J Neurosci 1999; 19:8979–89.PubMedGoogle Scholar
  153. 153.
    Rauch U, Feng K, Zhou XH. Neurocan: a brain chondroitin sulfate proteoglycan. Cell Mol Life Sci 2001; 58:1842–56.PubMedGoogle Scholar
  154. 154.
    Schmalfeldt M, Bandtlow CE, Dours-Zimmermann MT et al. Brain derived versican V2 is a potent inhibitor of axonal growth. J Cell Sci 2000; 113:807–16.PubMedGoogle Scholar
  155. 155.
    Chang A, Nishiyama A, Peterson J et al. NG2-positive oligodendrocyte progenitor cells in adult human brain and multiple sclerosis lesions. J Neurosci 2000; 20:6404–12.PubMedGoogle Scholar
  156. 156.
    Chen ZJ, Negra M, Levine A et al. Oligodendrocyte precursor cells: reactive cells inhibit axon growth and regeneration. J Neurocytol 2002; 31:481–95.PubMedGoogle Scholar
  157. 157.
    Dawson MR, Levine JM, Reynolds R. NG 2-expressing cells in the central nervous system: are they oligodendroglial progenitors? J Neurosci Res 2000; 61:471–9.PubMedGoogle Scholar
  158. 158.
    Greenwood K, Butt AM. Evidence that perinatal and adult NG2-glia are not conventional oligodendrocyte progenitors and do not depend on axons for their survival. Mol Cell Neurosci 2003; 23:544–58.PubMedGoogle Scholar
  159. 159.
    Mallon BS, Shick HE, Kidd GJ et al. Proteolipid promoter activity distinguishes two populations of NG2-positive cells throughout neonatal cortical development. J Neurosci 2002; 22:876–85.PubMedGoogle Scholar
  160. 160.
    Jones LL, Yamaguchi Y, Stallcup WB et al. NG2 is a major chondroitin sulfate proteoglycan produced after spinal cord injury and is expressed by macrophages and oligodendrocyte progenitors. J Neurosci 2002; 22:2792–803.PubMedGoogle Scholar
  161. 161.
    Asher RA, Morgenstern DA, Shearer MC et al. Versican is upregulated in CNS injury and is a product of oligodendrocyte lineage cells. J Neurosci 2002; 22:2225–36.PubMedGoogle Scholar
  162. 162.
    Tang X, Davies JE, Davies SJ. Changes in distribution, cell associations, and protein expression levels of NG2, neurocan, phosphacan, brevican, versican V2, and tenascin-C during acute to chronic maturation of spinal cord scar tissue. J Neurosci Res 2003; 71:427–44.PubMedGoogle Scholar
  163. 163.
    Davies SJ, Goucher DR, Doller C et al. Robust regeneration of adult sensory axons in degenerating white matter of the adult rat spinal cord. J Neurosci 1999; 19:5810–22.PubMedGoogle Scholar
  164. 164.
    Bradbury EJ, Moon LD, Popat RJ et al. Chondroitinase ABC promotes functional recovery after spinal cord injury. Nature 2002; 416:636–40.PubMedGoogle Scholar
  165. 165.
    Yick LW, Wu W et al. Chondroitinase ABC promotes axonal regeneration of Clarke’s neurons after spinal cord injury. Neuroreport 2000; 11:1063–67.PubMedGoogle Scholar
  166. 166.
    Moon LD, Asher RA et al. Regeneration of CNS axons back to their target following treatment of adult rat brain with chondroitinase ABC. Nat Neurosci 2001; 4:465–466.PubMedGoogle Scholar
  167. 167.
    Ajemian A, Ness R, David S. Tenascin in the injured rat optic nerve and in non-neuronal cells in vitro: potential role in neural repair. J Comp Neurol 1994; 340:233–42.PubMedGoogle Scholar
  168. 168.
    Chiquet-Ehrismann R. Tenascins. Int J Biochem Cell Biol 2004; 36:986–90.PubMedGoogle Scholar
  169. 169.
    Joester A, Faissner A. The structure and function of tenascins in the nervous system. Matrix Biol 2001; 20:13–22.PubMedGoogle Scholar
  170. 170.
    Pesheva P, Gloor S, Probstmeier R. Tenascin-R as a regulator of CNS glial cell function. Prog Brain Res 2001; 132:103–14.PubMedGoogle Scholar
  171. 171.
    Lochter A, Vaughan L, Kaplony A et al. J1/tenascin in substrate-bound and soluble form displays contrary effects on neurite outgrowth. J Cell Biol 1991; 113:1159–71.PubMedGoogle Scholar
  172. 172.
    Neidhardt J, Fehr S, Kutsche M, Lohler J et al. Tenascin-N: characterization of a novel member of the tenascin family that mediates neurite repulsion from hippocampal explants. Mol Cell Neurosci 2003; 23:193–209.PubMedGoogle Scholar
  173. 173.
    Probstmeier R, Braunewell K, Pesheva P. Involvement of chondroitin sulfates on brain-derived tenascin-R in carbohydrate-dependent interactions with fibronectin and tenascin-C. Brain Res 2000; 863:42–51.PubMedGoogle Scholar
  174. 174.
    de Wit J, Verhaagen J. Role of semaphorins in the adult nervous system. Prog Neurobiol 2003; 71:249–67.PubMedGoogle Scholar
  175. 175.
    Pasterkamp RJ, Verhaagen J. Emerging roles for semaphorins in neural regeneration. Brain Res Brain Res Rev 2001; 35:36–54.PubMedGoogle Scholar
  176. 176.
    Pasterkamp RJ, Kolodkin AL. Semaphorin junction: making tracks toward neural connectivity. Curr Opin Neurobiol 2003; 13:79–89.PubMedGoogle Scholar
  177. 177.
    De Winter F, Oudega M, Lankhorst AJ et al. Injury-induced class 3 semaphorin expression in the rat spinal cord. Exp Neurol 2002; 175:61–75.PubMedGoogle Scholar
  178. 178.
    Pasterkamp RJ, Giger RJ, Ruitenberg MJ et al. Expression of the gene encoding the chemorepellent semaphorin III is induced in the fibroblast component of neural scar tissue formed following injuries of adult but not neonatal CNS. Mol Cell Neurosci 1999; 13:143–66.PubMedGoogle Scholar
  179. 179.
    Niclou SP, Franssen EH, Ehlert EM et al. Meningeal cell-derived semaphorin 3A inhibits neurite outgrowth. Mol Cell Neurosci 2003; 24:902–12.PubMedGoogle Scholar
  180. 180.
    Moreau-Fauvarque C, Kumanogoh A, Camand E et al. The transmembrane semaphorin Sema4D/CD100, an inhibitor of axonal growth, is expressed on oligodendrocytes and upregulated after CNS lesion. J Neurosci 2003; 23:9229–39.PubMedGoogle Scholar
  181. 181.
    Goldberg JL, Vargas ME, Wang JT et al. An oligodendrocyte lineage-specific semaphorin, Sema5A, inhibits axon growth by retinal ganglion cells. J Neurosci 2004; 24:4989–99.PubMedGoogle Scholar
  182. 182.
    Fournier AE, GrandPre T, Strittmatter SM. Identification of a receptor mediating Nogo-66 inhibition of axonal regeneration. Nature 2001; 409:341–6.PubMedGoogle Scholar
  183. 183.
    Domeniconi M, Cao Z, Spencer T et al. Myelin-associated glycoprotein interacts with the Nogo66 receptor to inhibit neurite outgrowth. Neuron 2002; 35:283–90.PubMedGoogle Scholar
  184. 184.
    Liu BP, Fournier A, GrandPre T et al. Myelin-Associated Glycoprotein as a Functional Ligand for the Nogo-66 Receptor. Science 2002; 1073031.Google Scholar
  185. 185.
    Barton WA, Liu BP, Tzvetkova D et al. Structure and axon outgrowth inhibitor binding of the Nogo-66 receptor and related proteins. Embo J 2003; 22:3291–302.PubMedGoogle Scholar
  186. 186.
    He XL, Bazan JF, McDermott G et al. Structure of the Nogo receptor ectodomain: a recognition module implicated in myelin inhibition. Neuron 2003; 38:177–85.PubMedGoogle Scholar
  187. 187.
    Venkatesh K, Chivatakarn O, Lee H et al. The Nogo-66 receptor homolog NgR2 is a sialic acid-dependent receptor selective for myelin-associated glycoprotein. J Neurosci 2005; 25:808–22.PubMedGoogle Scholar
  188. 188.
    Wang KC, Kim JA, Sivasankaran R et al. P75 interacts with the Nogo receptor as a co-receptor for Nogo, MAG and OMgp. Nature 2002; 420:74–8.PubMedGoogle Scholar
  189. 189.
    Wong ST, Henley JR, Kanning KC et al. A p75(NTR) and Nogo receptor complex mediates repulsive signaling by myelin-associated glycoprotein. Nat Neurosci 2002; 5:1302–8.PubMedGoogle Scholar
  190. 190.
    Mi S, Lee X, Shao Z et al. LINGO-1 is a component of the Nogo-66 receptor/p75 signaling complex. Nat Neurosci 2004; 7:221–8.PubMedGoogle Scholar
  191. 191.
    Schweigreiter R, Walmsley AR, Niederost B et al. Versican V2 and the central inhibitory domain of Nogo-A inhibit neurite growth via p75NTR/NgR-independent pathways that converge at RhoA. Mol Cell Neurosci 2004; 27:163–74.PubMedGoogle Scholar
  192. 192.
    Yamashita T, Higuchi H, Tohyama M. The p75 receptor transduces the signal from myelin-associated glycoprotein to Rho. J Cell Biol 2002; 157:565–70.PubMedGoogle Scholar
  193. 193.
    Park JB, Yiu G, Kaneko S et al. A TNF receptor family member, TROY, is a coreceptor with Nogo receptor in mediating the inhibitory activity of myelin inhibitors. Neuron 2005; 45:345–51.PubMedGoogle Scholar
  194. 194.
    Shao Z, Browning JL, Lee X et al. TAJ/TROY, an orphan TNF receptor family member, binds Nogo-66 receptor 1 and regulates axonal regeneration. Neuron 2005; 45:353–9.PubMedGoogle Scholar
  195. 195.
    McKerracher L. Ganglioside rafts as MAG receptors that mediate blockade of axon growth. Proc Natl Acad Sci USA 2002; 99:7811–3.PubMedGoogle Scholar
  196. 196.
    Vinson M, Strijbos PJ, Rowles A et al. Myelin-associated glycoprotein interacts with ganglioside GT1b. A mechanism for neurite outgrowth inhibition. J Biol Chem 2001; 276:20280–5.PubMedGoogle Scholar
  197. 197.
    Vyas AA, Patel HV, Fromholt SE et al. Gangliosides are functional nerve cell ligands for myelin-associated glycoprotein (MAG), an inhibitor of nerve regeneration. Proc Natl Acad Sci USA 2002; 99:8412–7.PubMedGoogle Scholar
  198. 198.
    Yang LJ, Zeller CB, Shaper NL et al. Gangliosides are neuronal ligands for myelin-associated glycoprotein. Proc Natl Acad Sci USA 1996; 93:814–8.PubMedGoogle Scholar
  199. 199.
    Etienne-Manneville S, Hall A. Integrin-mediated activation of Cdc42 controls cell polarity in migrating astrocytes through PKCzeta. Cell 2001; 106:489–98.PubMedGoogle Scholar
  200. 200.
    Lehmann M, Fournier A, Selles-Navarro I et al. Inactivation of Rho signaling pathway promotes CNS axon regeneration. J Neurosci 1999; 19:7537–47.PubMedGoogle Scholar
  201. 201.
    Niederost B, Oertle T, Fritsche J et al. Nogo-A and myelin-associated glycoprotein mediate neurite growth inhibition by antagonistic regulation of RhoA and Rac1. J Neurosci 2002; 22:10368–76.PubMedGoogle Scholar
  202. 202.
    Dergham P, Ellezam B, Essagian C et al. Rho signaling pathway targeted to promote spinal cord repair. J Neurosci 2002; 22:6570–7.PubMedGoogle Scholar
  203. 203.
    Monnier PP, Sierra A, Schwab JM et al. The Rho/ROCK pathway mediates neurite growth-inhibitory activity associated with the chondroitin sulfate proteoglycans of the CNS glial scar. Mol Cell Neurosci 2003; 22:319–30.PubMedGoogle Scholar
  204. 204.
    Yamashita T, Tucker KL, Barde YA. Neurotrophin binding to the p75 receptor modulates Rho activity and axonal outgrowth. Neuron 1999; 24:585–93.PubMedGoogle Scholar
  205. 205.
    Yamashita T, Tohyama M. The p75 receptor acts as a displacement factor that releases Rho from Rho-GDI. Nat Neurosci 2003; 6:461–7.PubMedGoogle Scholar
  206. 206.
    Borisoff JF, Chan CC, Hiebert GW et al. Suppression of Rho-kinase activity promotes axonal growth on inhibitory CNS substrates. Mol Cell Neurosci 2003; 22:405–16.PubMedGoogle Scholar
  207. 207.
    Fournier AE, Takizawa BT, Strittmatter SM. Rho kinase inhibition enhances axonal regeneration in the injured CNS. J Neurosci 2003; 23:1416–23.PubMedGoogle Scholar
  208. 208.
    Riento K, Ridley AJ. Rocks: multifunctional kinases in cell behaviour. Nat Rev Mol Cell Biol 2003; 4:446–56.PubMedGoogle Scholar
  209. 209.
    Qiu J, Cai D, Dai H et al. Spinal axon regeneration induced by elevation of cyclic AMP. Neuron 2002; 34:895–903.PubMedGoogle Scholar
  210. 210.
    Gao Y, Deng K, Hou J et al. Activated CREB is sufficient to overcome inhibitors in myelin and promote spinal axon regeneration in vivo. Neuron 2004; 44:609–21.PubMedGoogle Scholar
  211. 211.
    Spencer T, Filbin MT. A role for cAMP in regeneration of the adult mammalian CNS. J Anat 2004; 204:49–55.PubMedGoogle Scholar
  212. 212.
    Nikulina E, Tidwell JL, Dai HN et al. The phosphodiesterase inhibitor rolipram delivered after a spinal cord lesion promotes axonal regeneration and functional recovery. Proc Natl Acad Sci USA 2004; 101:8786–90.PubMedGoogle Scholar
  213. 213.
    Ellezam B, Dubreuil C, Winton M et al. Inactivation of intracellular Rho to stimulate axon growth and regeneration. Prog Brain Res 2002; 137:371–80.PubMedGoogle Scholar
  214. 214.
    Strittmatter S.M. Modulation of axonal regeneration in neurodegenerative disease: focus on Nogo. J Mol Neurosci 2002; 19:117–21.PubMedGoogle Scholar
  215. 215.
    Boyd JG, Doucette R, Kawaja MD. Defining the role of olfactory ensheathing cells in facilitating axon remyelination following damage to the spinal cord. Faseb J 2005; 19:694–703.PubMedGoogle Scholar
  216. 216.
    Reier PJ. Cellular Transplantation Strategies for Spinal Cord Injury and Translational Neurobiology. Neurorx 2004; 1:424–451.PubMedGoogle Scholar
  217. 217.
    Barnett SC. Olfactory ensheathing cells: unique glial cell types? J Neurotrauma 2004; 21:375–82.PubMedGoogle Scholar
  218. 218.
    Bunge MB, Pearse DD. Transplantation strategies to promote repair of the injured spinal cord. J Rehabil Res Dev 2003; 40:55–62.PubMedGoogle Scholar
  219. 219.
    Jones DG, Anderson ER, Galvin KA. Spinal cord regeneration: moving tentatively towards new perspectives. NeuroRehabilitation 2003; 18:339–51.PubMedGoogle Scholar
  220. 220.
    Hendriks WT, Ruitenberg MJ, Blits B et al. Viral vector-mediated gene transfer of neurotrophins to promote regeneration of the injured spinal cord. Prog Brain Res 2004; 146:451–76.PubMedGoogle Scholar
  221. 221.
    Barnett SC, Chang L. Olfactory ensheathing cells and CNS repair: going solo or in need of a friend? Trends Neurosci 2004; 27:54–60.PubMedGoogle Scholar
  222. 222.
    Barnett SC, Riddell JS. Olfactory ensheathing cells (OECs) and the treatment of CNS injury: advantages and possible caveats. J Anat 2004; 204:57–67.PubMedGoogle Scholar
  223. 223.
    Nieto-Sampedro M. Central nervous system lesions that can and those that cannot be repaired with the help of olfactory bulb ensheathing cell transplants. Neurochem Res 2003; 28:1659–76.PubMedGoogle Scholar
  224. 224.
    Santos-Benito FF, Ramon-Cueto A. Olfactory ensheathing glia transplantation: a therapy to promote repair in the mammalian central nervous system. Anat Rec B New Anat 2003; 271:77–85.PubMedGoogle Scholar
  225. 225.
    Blits B, Boer GJ, Verhaagen J. Pharmacological, cell, and gene therapy strategies to promote spinal cord regeneration. Cell Transplant 2002; 11:593–613.PubMedGoogle Scholar
  226. 226.
    Raisman G. Olfactory ensheathing cells-another miracle cure for spinal cord injury? Nat Rev Neurosci 2001; 2:369–75.PubMedGoogle Scholar
  227. 227.
    Fry EJ. Central nervous system regeneration: mission impossible? Clin Exp Pharmacol Physiol 2001; 28:253–8.PubMedGoogle Scholar
  228. 228.
    Stichel CC, Hermanns S, Luhmann HJ et al. Inhibition of collagen IV deposition promotes regeneration of injured CNS axons. Eur J Neurosci 1999; 11:632–646.PubMedGoogle Scholar
  229. 229.
    Blesch A, Lu P, Tuszynski MH. Neurotrophic factors, gene therapy, and neural stem cells for spinal cord repair. Brain Res Bull 2002; 57:833–8.PubMedGoogle Scholar
  230. 230.
    David S, Lacroix S. Molecular approaches to spinal cord repair. Annu Rev Neurosci 2003; 26:411–40.PubMedGoogle Scholar
  231. 231.
    Fournier AE, Gould GC, Liu BP et al. Truncated soluble Nogo receptor binds Nogo-66 and blocks inhibition of axon growth by myelin. J Neurosci 2002; 22:8876–83.PubMedGoogle Scholar
  232. 232.
    Li S, Liu BP, Budel S et al. Blockade of Nogo-66, myelin-associated glycoprotein, and oligodendrocyte myelin glycoprotein by soluble Nogo-66 receptor promotes axonal sprouting and recovery after spinal injury. J Neurosci 2004 24:10511–20.PubMedGoogle Scholar
  233. 233.
    Stichel CC, Lausberg F, Hermanns S et al. Scar modulation in subacute and chronic CNS lesions: Effects on axonal regeneration. Restor Neurol Neursoci 1999; 15:1–15.Google Scholar
  234. 234.
    Hermanns S, Reiprich P, Muller HW. A reliable method to reduce collagen scar formation in the lesioned rat spinal cord. J Neurosci Methods 2001; 110:141–6.PubMedGoogle Scholar
  235. 235.
    Weidner N, Grill RJ, Tuszynski MH. Elimination of basal lamina and the collagen “scar” after spinal cord injury fails to augment corticospinal tract regeneration. Exp Neurol 1999; 160:40–50.PubMedGoogle Scholar
  236. 236.
    Lemons ML, Howland DR, Anderson DK. Chondroitin sulfate proteoglycan immunoreactivity increases following spinal cord injury and transplantation. Exp Neurol 1999; 160:51–65.PubMedGoogle Scholar
  237. 237.
    Raineteau O, Schwab ME. Plasticity of motor systems after incomplete spinal cord injury. Nat Rev Neurosci 2001; 2:263–73.PubMedGoogle Scholar

Copyright information

© and Kluwer Academic / Plenum Publishers 2006

Authors and Affiliations

  • Anne D. Zurn
    • 1
  • Christine E. Bandtlow
    • 2
  1. 1.Department of Experimental SurgeryLausanne University Hospital Faculty of Biology and MedicineLausanneSwitzerland
  2. 2.Biocenter Innsbruck Division of NeurobiochemistryInnsbruck Medical UniversityInnsbruckAustria

Personalised recommendations