Extrinsic and intrinsic factors controlling axonal regeneration after spinal cord injury

Fardad T. Afshari; Sunil Kappagantula; James W. Fawcett

doi:10.1017/S1462399409001288

Extrinsic and intrinsic factors controlling axonal regeneration after spinal cord injury

Published online by Cambridge University Press: 08 December 2009

Fardad T. Afshari ,

Sunil Kappagantula and

James W. Fawcett

Show author details

Fardad T. Afshari*: Affiliation:
Centre for Brain Repair, University of Cambridge, Cambridge, UK.
Sunil Kappagantula: Affiliation:
Centre for Brain Repair, University of Cambridge, Cambridge, UK.
James W. Fawcett: Affiliation:
Centre for Brain Repair, University of Cambridge, Cambridge, UK.
*: *Corresponding author: Fardad T. Afshari, Centre for Brain Repair, University of Cambridge, Forvie Site, Robinson Way, Cambridge, CB2 0PY, UK. Tel: +44 1223 334121; Fax: +44 1223 331174; E-mail: ft218@cam.ac.uk

Article contents

Abstract
References

Get access

Rights & Permissions

Abstract

Spinal cord injury is one of the most devastating conditions that affects the central nervous system. It can lead to permanent disability and there are around two million people affected worldwide. After injury, accumulation of myelin debris and formation of an inhibitory glial scar at the site of injury leads to a physical and chemical barrier that blocks axonal growth and regeneration. The mammalian central nervous system thus has a limited intrinsic ability to repair itself after injury. To improve axonal outgrowth and promote functional recovery, it is essential to identify the various intrinsic and extrinsic factors controlling regeneration and navigation of axons within the inhibitory environment of the central nervous system. Recent advances in spinal cord research have opened new avenues for the exploration of potential targets for repairing the cord and improving functional recovery after trauma. Here, we discuss some of the important key molecules that could be harnessed for repairing spinal cord injury.

Type: Review Article
Information: Expert Reviews in Molecular Medicine , Volume 11 , July 2009 , e37

DOI: https://doi.org/10.1017/S1462399409001288 [Opens in a new window]
Copyright: Copyright © Cambridge University Press 2009

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1Oudega, M. (2007) Schwann cell and olfactory ensheathing cell implantation for repair of the contused spinal cord. Acta Physiologica 189, 181-189CrossRef Google Scholar PubMed

2Kwon, B.K., Borisoff, J.F. and Tetzlaff, W. (2002) Molecular targets for therapeutic intervention after spinal cord injury. Molecular Interventions 2, 244-258CrossRef Google Scholar PubMed

3Silver, J. and Miller, J.H. (2004) Regeneration beyond the glial scar. Nature Reviews Neuroscience 5, 146-156CrossRef Google Scholar PubMed

4Fawcett, J.W. and Asher, R.A. (1999) The glial scar and central nervous system repair. Brain Research Bulletin 49, 377-391CrossRef Google Scholar PubMed

5Okada, S. et al. (2004) Blockade of interleukin-6 receptor suppresses reactive astrogliosis and ameliorates functional recovery in experimental spinal cord injury. Journal of Neuroscience Research 76, 265-276CrossRef Google Scholar PubMed

6Nakamura, M. et al. (2005) Role of IL-6 in spinal cord injury in a mouse model. Clinical Reviews in Allergy and Immunology 28, 197-204CrossRef Google Scholar PubMed

7Faulkner, J.R. et al. (2004) Reactive astrocytes protect tissue and preserve function after spinal cord injury. Journal of Neuroscience 24, 2143-2155CrossRef Google Scholar PubMed

8Bundesen, L.Q. et al. (2003) Ephrin-B2 and EphB2 regulation of astrocyte-meningeal fibroblast interactions in response to spinal cord lesions in adult rats. Journal of Neuroscience 23, 7789-7800CrossRef Google Scholar PubMed

9Abnet, K., Fawcett, J.W. and Dunnett, S.B. (1991) Interactions between meningeal cells and astrocytes in vivo and in vitro. Brain Research Developmental Brain Research 59, 187-196CrossRef Google Scholar PubMed

10Windle, W.F., Clemente, C.D. and Chambers, W.W. (1952) Inhibition of formation of a glial barrier as a means of permitting a peripheral nerve to grow into the brain. Journal of Comparative Neurology 96, 359-369CrossRef Google Scholar PubMed

11Kwok, J.C. et al. (2008) Proteoglycans in the central nervous system: Plasticity, regeneration and their stimulation with chondroitinase ABC. Restorative Neurology and Neuroscience 26, 131-145Google Scholar PubMed

12Niclou, S.P., Ehlert, E.M. and Verhaagen, J. (2006) Chemorepellent axon guidance molecules in spinal cord injury. Journal of Neurotrauma 23, 409-421CrossRef Google Scholar PubMed

13Asher, R.A. et al. (2000) Neurocan is upregulated in injured brain and in cytokine-treated astrocytes. Journal of Neuroscience 20, 2427-2438CrossRef Google Scholar PubMed

14Yong, V.W. et al. (1991) Gamma-interferon promotes proliferation of adult human astrocytes in vitro and reactive gliosis in the adult mouse brain in vivo. Proceedings of the National Academy of Sciences of the United States of America 88, 7016-7020CrossRef Google Scholar PubMed

15Giulian, D. et al. (1988) Interleukin-1 injected into mammalian brain stimulates astrogliosis and neovascularization. Journal of Neuroscience 8, 2485-2490CrossRef Google Scholar PubMed

16Grados-Munro, E.M. and Fournier, A.E. (2003) Myelin-associated inhibitors of axon regeneration. Journal of Neuroscience Research 74, 479-485CrossRef Google Scholar PubMed

17McGee, A.W. and Strittmatter, S.M. (2003) The Nogo-66 receptor: focusing myelin inhibition of axon regeneration. Trends in Neurosciences 26, 193-198CrossRef Google Scholar PubMed

18Caroni, P. and Schwab, M.E. (1988) Two membrane protein fractions from rat central myelin with inhibitory properties for neurite growth and fibroblast spreading. Journal of Cell Biology 106, 1281-1288CrossRef Google Scholar PubMed

19Caroni, P. and Schwab, M.E. (1988) Antibody against myelin-associated inhibitor of neurite growth neutralizes nonpermissive substrate properties of CNS white matter. Neuron 1, 85-96CrossRef Google Scholar PubMed

20Schnell, L. and Schwab, M.E. (1990) Axonal regeneration in the rat spinal cord produced by an antibody against myelin-associated neurite growth inhibitors. Nature 343, 269-272CrossRef Google Scholar PubMed

21Fouad, K., Klusman, I. and Schwab, M.E. (2004) Regenerating corticospinal fibers in the Marmoset (Callitrix jacchus) after spinal cord lesion and treatment with the anti-Nogo-A antibody IN-1. European Journal of Neuroscience 20, 2479-2482CrossRef Google Scholar PubMed

22Freund, P. et al. (2006) Nogo-A-specific antibody treatment enhances sprouting and functional recovery after cervical lesion in adult primates. Nature Medicine 12, 790-792CrossRef Google Scholar PubMed

23Blight, A.R. and Tuszynski, M.H. (2006) Clinical trials in spinal cord injury. Journal of Neurotrauma 23, 586-593CrossRef Google Scholar PubMed

24Chen, M.S. et al. (2000) Nogo-A is a myelin-associated neurite outgrowth inhibitor and an antigen for monoclonal antibody IN-1. Nature 403, 434-439CrossRef Google Scholar

25Hu, F. and Strittmatter, S.M. (2008) The N-terminal domain of Nogo-A inhibits cell adhesion and axonal outgrowth by an integrin-specific mechanism. Journal of Neuroscience 28, 1262-1269CrossRef Google Scholar PubMed

26Fournier, A.E., GrandPre, T. and Strittmatter, S.M. (2001) Identification of a receptor mediating Nogo-66 inhibition of axonal regeneration. Nature 409, 341-346CrossRef Google Scholar PubMed

27Wang, K.C. et al. (2002) P75 interacts with the Nogo receptor as a co-receptor for Nogo, MAG and OMgp. Nature 420, 74-78CrossRef Google Scholar PubMed

28Mosyak, L. et al. (2006) The structure of the Lingo-1 ectodomain, a module implicated in central nervous system repair inhibition. Journal of Biological Chemistry 281, 36378-36390CrossRef Google Scholar PubMed

29GrandPre, T., Li, S. and Strittmatter, S.M. (2002) Nogo-66 receptor antagonist peptide promotes axonal regeneration. Nature 417, 547-551CrossRef Google Scholar PubMed

30Zheng, B. et al. (2003) Lack of enhanced spinal regeneration in Nogo-deficient mice. Neuron 38, 213-224CrossRef Google Scholar PubMed

31Simonen, M. et al. (2003) Systemic deletion of the myelin-associated outgrowth inhibitor Nogo-A improves regenerative and plastic responses after spinal cord injury. Neuron 38, 201-211CrossRef Google Scholar PubMed

32Kim, J.E. et al. (2003) Axon regeneration in young adult mice lacking Nogo-A/B. Neuron 38, 187-199CrossRef Google Scholar PubMed

33Lee, J.K. et al. (2009) Reassessment of corticospinal tract regeneration in Nogo-deficient mice. Journal of Neuroscience 29, 8649-8654CrossRef Google Scholar PubMed

34Martini, R. (1994) Expression and functional roles of neural cell surface molecules and extracellular matrix components during development and regeneration of peripheral nerves. Journal of Neurocytology 23, 1-28CrossRef Google Scholar PubMed

35Mukhopadhyay, G. et al. (1994) A novel role for myelin-associated glycoprotein as an inhibitor of axonal regeneration. Neuron 13, 757-767CrossRef Google Scholar PubMed

36McKerracher, L. et al. (1994) Identification of myelin-associated glycoprotein as a major myelin-derived inhibitor of neurite growth. Neuron 13, 805-811CrossRef Google Scholar

37Schnaar, R.L. and Lopez, P.H. (2009) Myelin-associated glycoprotein and its axonal receptors. Journal of Neuroscience Research 87, 3267-3276CrossRef Google Scholar PubMed

38Mehta, N.R. et al. (2007) Gangliosides and Nogo receptors independently mediate myelin-associated glycoprotein inhibition of neurite outgrowth in different nerve cells. Journal of Biological Chemistry 282, 27875-27886CrossRef Google Scholar PubMed

39Domeniconi, M. et al. (2002) Myelin-associated glycoprotein interacts with the Nogo66 receptor to inhibit neurite outgrowth. Neuron 35, 283-290CrossRef Google Scholar PubMed

40Mikol, D.D. and Stefansson, K. (1988) A phosphatidylinositol-linked peanut agglutinin-binding glycoprotein in central nervous system myelin and on oligodendrocytes. Journal of Cell Biology 106, 1273-1279CrossRef Google Scholar PubMed

41Kottis, V. et al. (2002) Oligodendrocyte-myelin glycoprotein (OMgp) is an inhibitor of neurite outgrowth. Journal of Neurochemistry 82, 1566-1569CrossRef Google Scholar PubMed

42Wang, K.C. et al. (2002) Oligodendrocyte-myelin glycoprotein is a Nogo receptor ligand that inhibits neurite outgrowth. Nature 417, 941-944CrossRef Google Scholar PubMed

43Niederost, B. et al. (2002) Nogo-A and myelin-associated glycoprotein mediate neurite growth inhibition by antagonistic regulation of RhoA and Rac1. Journal of Neuroscience 22, 10368-10376CrossRef Google Scholar PubMed

44Yamashita, T. et al. (2005) Multiple signals regulate axon regeneration through the Nogo receptor complex. Molecular Neurobiology 32, 105-111CrossRef Google Scholar PubMed

45Gallo, V., Bertolotto, A. and Levi, G. (1987) The proteoglycan chondroitin sulfate is present in a subpopulation of cultured astrocytes and in their precursors. Developmental Biology 123, 282-285CrossRef Google Scholar

46Johnson-Green, P.C., Dow, K.E. and Riopelle, R.J. (1991) Characterization of glycosaminoglycans produced by primary astrocytes in vitro. Glia 4, 314-321CrossRef Google Scholar PubMed

47Crespo, D. et al. (2007) How does chondroitinase promote functional recovery in the damaged CNS? Experimental Neurology 206, 159-171CrossRef Google Scholar PubMed

48Dou, C.L. and Levine, J.M. (1994) Inhibition of neurite growth by the NG2 chondroitin sulfate proteoglycan. Journal of Neuroscience 14, 7616-7628CrossRef Google Scholar PubMed

49McKeon, R.J., Hoke, A. and Silver, J. (1995) Injury-induced proteoglycans inhibit the potential for laminin-mediated axon growth on astrocytic scars. Experimental Neurology 136, 32-43CrossRef Google Scholar PubMed

50Moon, L.D. et al. (2001) Regeneration of CNS axons back to their target following treatment of adult rat brain with chondroitinase ABC. Nature Neuroscience 4, 465-466CrossRef Google Scholar PubMed

51Caggiano, A.O. et al. (2005) Chondroitinase ABCI improves locomotion and bladder function following contusion injury of the rat spinal cord. Journal of Neurotrauma 22, 226-239CrossRef Google Scholar PubMed

52Bradbury, E.J. et al. (2002) Chondroitinase ABC promotes functional recovery after spinal cord injury. Nature 416, 636-640CrossRef Google Scholar PubMed

53Cafferty, W.B. et al. (2007) Functional axonal regeneration through astrocytic scar genetically modified to digest chondroitin sulfate proteoglycans. Journal of Neuroscience 27, 2176-2185CrossRef Google Scholar PubMed

54Yada, T. et al. (2003) Chondroitin sulfate synthase-2. Molecular cloning and characterization of a novel human glycosyltransferase homologous to chondroitin sulfate glucuronyltransferase, which has dual enzymatic activities. Journal of Biological Chemistry 278, 30235-30247CrossRef Google Scholar PubMed

55Kitagawa, H. et al. (1997) Regulation of chondroitin sulfate biosynthesis by specific sulfation: acceptor specificity of serum beta-GalNAc transferase revealed by structurally defined oligosaccharides. Glycobiology 7, 531-537CrossRef Google Scholar PubMed

56Laabs, T.L. et al. (2007) Inhibiting glycosaminoglycan chain polymerization decreases the inhibitory activity of astrocyte-derived chondroitin sulfate proteoglycans. Journal of Neuroscience 27, 14494-14501CrossRef Google Scholar PubMed

57Zhou, F.Q. et al. (2006) Neurotrophins support regenerative axon assembly over CSPGs by an ECM-integrin-independent mechanism. Journal of Cell Science 119, 2787-2796CrossRef Google Scholar PubMed

58Smith-Thomas, L.C. et al. (1994) An inhibitor of neurite outgrowth produced by astrocytes. Journal of Cell Science 107, 1687-1695CrossRef Google Scholar PubMed

59Yamaguchi, Y., Mann, D.M. and Ruoslahti, E. (1990) Negative regulation of transforming growth factor-beta by the proteoglycan decorin. Nature 346, 281-284CrossRef Google Scholar PubMed

60Davies, J.E. et al. (2004) Decorin suppresses neurocan, brevican, phosphacan and NG2 expression and promotes axon growth across adult rat spinal cord injuries. European Journal of Neuroscience 19, 1226-1242CrossRef Google Scholar PubMed

61Santra, M., Reed, C.C. and Iozzo, R.V. (2002) Decorin binds to a narrow region of the epidermal growth factor (EGF) receptor, partially overlapping but distinct from the EGF-binding epitope. Journal of Biological Chemistry 277, 35671-35681CrossRef Google Scholar PubMed

62Minor, K. et al. (2008) Decorin promotes robust axon growth on inhibitory CSPGs and myelin via a direct effect on neurons. Neurobiology of Disease 32, 88-95CrossRef Google Scholar

63Zou, Y. et al. (2000) Squeezing axons out of the gray matter: a role for slit and semaphorin proteins from midline and ventral spinal cord. Cell 102, 363-375CrossRef Google Scholar PubMed

64Raper, J.A. (2000) Semaphorins and their receptors in vertebrates and invertebrates. Current Opinion in Neurobiology 10, 88-94CrossRef Google Scholar PubMed

65Pasterkamp, R.J., Anderson, P.N. and Verhaagen, J. (2001) Peripheral nerve injury fails to induce growth of lesioned ascending dorsal column axons into spinal cord scar tissue expressing the axon repellent Semaphorin3A. European Journal of Neuroscience 13, 457-471CrossRef Google Scholar PubMed

66Pasterkamp, R.J., Giger, R.J. and Verhaagen, J. (1998) Regulation of semaphorin III/collapsin-1 gene expression during peripheral nerve regeneration. Experimental Neurology 153, 313-327CrossRef Google Scholar PubMed

67Kikuchi, K. et al. (2003) In vitro and in vivo characterization of a novel semaphorin 3A inhibitor, SM-216289 or xanthofulvin. Journal of Biological Chemistry 278, 42985-42991CrossRef Google Scholar PubMed

68Kaneko, S. et al. (2006) A selective Sema3A inhibitor enhances regenerative responses and functional recovery of the injured spinal cord. Nature Medicine 12, 1380-1389CrossRef Google Scholar PubMed

69Klein, R. (2004) Eph/ephrin signaling in morphogenesis, neural development and plasticity. Current Opinion in Cell Biology 16, 580-589CrossRef Google Scholar PubMed

70Goldshmit, Y., McLenachan, S. and Turnley, A. (2006) Roles of Eph receptors and ephrins in the normal and damaged adult CNS. Brain Research Reviews 52, 327-345CrossRef Google Scholar PubMed

71Gale, N.W. et al. (1996) Eph receptors and ligands comprise two major specificity subclasses and are reciprocally compartmentalized during embryogenesis. Neuron 17, 9-19CrossRef Google Scholar PubMed

72Torres, R. et al. (1998) PDZ proteins bind, cluster, and synaptically colocalize with Eph receptors and their ephrin ligands. Neuron 21, 1453-1463CrossRef Google Scholar PubMed

73Kullander, K. and Klein, R. (2002) Mechanisms and functions of Eph and ephrin signalling. Nature Reviews Molecular Cell Biology 3, 475-486CrossRef Google Scholar PubMed

74Gao, P.P. et al. (1998) Regulation of thalamic neurite outgrowth by the Eph ligand ephrin-A5: implications in the development of thalamocortical projections. Proceedings of the National Academy of Sciences of the United States of America 95, 5329-5334CrossRef Google Scholar PubMed

75Kullander, K. et al. (2001) Ephrin-B3 is the midline barrier that prevents corticospinal tract axons from recrossing, allowing for unilateral motor control. Genes and Development 15, 877-888CrossRef Google Scholar PubMed

76Benson, M.D. et al. (2005) Ephrin-B3 is a myelin-based inhibitor of neurite outgrowth. Proceedings of the National Academy of Sciences of the United States of America 102, 10694-10699CrossRef Google Scholar PubMed

77Willson, C.A. et al. (2002) Upregulation of EphA receptor expression in the injured adult rat spinal cord. Cell Transplantation 11, 229-239CrossRef Google Scholar PubMed

78Miranda, J.D. et al. (1999) Induction of Eph B3 after spinal cord injury. Experimental Neurology 156, 218-222CrossRef Google Scholar PubMed

79Fabes, J. et al. (2006) Accumulation of the inhibitory receptor EphA4 may prevent regeneration of corticospinal tract axons following lesion. European Journal of Neuroscience 23, 1721-1730CrossRef Google Scholar PubMed

80Kliffen, M. et al. (1997) Increased expression of angiogenic growth factors in age-related maculopathy. British Journal of Ophthalmology 81, 154-162CrossRef Google Scholar PubMed

81Goldshmit, Y. et al. (2004) Axonal regeneration and lack of astrocytic gliosis in EphA4-deficient mice. Journal of Neuroscience 24, 10064-10073CrossRef Google Scholar PubMed

82Fabes, J. et al. (2007) Regeneration-enhancing effects of EphA4 blocking peptide following corticospinal tract injury in adult rat spinal cord. European Journal of Neuroscience 26, 2496-2505CrossRef Google Scholar PubMed

83Lawrenson, I.D. et al. (2002) Ephrin-A5 induces rounding, blebbing and de-adhesion of EphA3-expressing 293T and melanoma cells by CrkII and Rho-mediated signalling. Journal of Cell Science 115, 1059-1072CrossRef Google Scholar PubMed

84Miao, H. et al. (2000) Activation of EphA2 kinase suppresses integrin function and causes focal-adhesion-kinase dephosphorylation. Nature Cell Biology 2, 62-69CrossRef Google Scholar PubMed

85Yamaguchi, Y. et al. (2001) RhoA inhibits the nerve growth factor-induced Rac1 activation through Rho-associated kinase-dependent pathway. Journal of Biological Chemistry 276, 18977-18983CrossRef Google Scholar PubMed

86Rutishauser, U. (2008) Polysialic acid in the plasticity of the developing and adult vertebrate nervous system. Nature Reviews Neuroscience 9, 26-35CrossRef Google Scholar PubMed

87Finne, J. et al. (1983) Occurrence of alpha 2–8 linked polysialosyl units in a neural cell adhesion molecule. Biochemical and Biophysical Research Communications 112, 482-487CrossRef Google Scholar

88Kiss, J.Z. et al. (2001) The role of neural cell adhesion molecules in plasticity and repair. Brain Research Reviews 36, 175-184CrossRef Google Scholar PubMed

89Becker, C.G. et al. (1996) The polysialic acid modification of the neural cell adhesion molecule is involved in spatial learning and hippocampal long-term potentiation. Journal of Neuroscience Research 45, 143-1523.0.CO;2-A>CrossRef Google Scholar PubMed

90Hoyk, Z., Parducz, A. and Theodosis, D.T. (2001) The highly sialylated isoform of the neural cell adhesion molecule is required for estradiol-induced morphological synaptic plasticity in the adult arcuate nucleus. European Journal of Neuroscience 13, 649-656CrossRef Google Scholar PubMed

91Hu, H. et al. (1996) The role of polysialic acid in migration of olfactory bulb interneuron precursors in the subventricular zone. Neuron 16, 735-743CrossRef Google Scholar PubMed

92Dusart, I. et al. (1999) Late axonal sprouting of injured Purkinje cells and its temporal correlation with permissive changes in the glial scar. Journal of Comparative Neurology 408, 399-4183.0.CO;2-2>CrossRef Google Scholar PubMed

93El Maarouf, A., Petridis, A.K. and Rutishauser, U. (2006) Use of polysialic acid in repair of the central nervous system. Proceedings of the National Academy of Sciences of the United States of America 103, 16989-16994CrossRef Google Scholar PubMed

94Zhang, Y. et al. (2007) Induced expression of polysialic acid in the spinal cord promotes regeneration of sensory axons. Molecular and Cellular Neurosciences 35, 109-119CrossRef Google Scholar PubMed

95Zhang, Y. et al. (2007) Lentiviral-mediated expression of polysialic acid in spinal cord and conditioning lesion promote regeneration of sensory axons into spinal cord. Molecular Therapy 15, 1796-1804CrossRef Google Scholar PubMed

96Marino, P. et al. (2009) A polysialic acid mimetic peptide promotes functional recovery in a mouse model of spinal cord injury. Experimental Neurology 219, 163-174CrossRef Google Scholar

97Lu, P. and Tuszynski, M.H. (2008) Growth factors and combinatorial therapies for CNS regeneration. Experimental Neurology 209, 313-320CrossRef Google Scholar PubMed

98Ramer, M.S., Priestley, J.V. and McMahon, S.B. (2000) Functional regeneration of sensory axons into the adult spinal cord. Nature 403, 312-316CrossRef Google Scholar PubMed

99Kobayashi, N.R. et al. (1997) BDNF and NT-4/5 prevent atrophy of rat rubrospinal neurons after cervical axotomy, stimulate GAP-43 and Talpha1-tubulin mRNA expression, and promote axonal regeneration. Journal of Neuroscience 17, 9583-9595CrossRef Google Scholar PubMed

100Schnell, L. et al. (1994) Neurotrophin-3 enhances sprouting of corticospinal tract during development and after adult spinal cord lesion. Nature 367, 170-173CrossRef Google Scholar PubMed

101Blesch, A. et al. (2004) Axonal responses to cellularly delivered NT-4/5 after spinal cord injury. Molecular and Cellular Neurosciences 27, 190-201CrossRef Google Scholar PubMed

102Blesch, A. and Tuszynski, M.H. (2003) Cellular GDNF delivery promotes growth of motor and dorsal column sensory axons after partial and complete spinal cord transections and induces remyelination. Journal of Comparative Neurology 467, 403-417CrossRef Google Scholar PubMed

103Bennett, D.L. et al. (2006) Artemin has potent neurotrophic actions on injured C-fibres. Journal of the Peripheral Nervous System 11, 330-345CrossRef Google Scholar PubMed

104Zhou, Z. et al. (2009) HSV-mediated transfer of artemin overcomes myelin inhibition to improve outcome after spinal cord injury. Molecular Therapy 17, 1173-1179CrossRef Google Scholar PubMed

105Park, S. and Hong, Y.W. (2006) Transcriptional regulation of artemin is related to neurite outgrowth and actin polymerization in mature DRG neurons. Neuroscience Letters 404, 61-66CrossRef Google Scholar PubMed

106Paveliev, M., Airaksinen, M.S. and Saarma, M. (2004) GDNF family ligands activate multiple events during axonal growth in mature sensory neurons. Molecular and Cellular Neurosciences 25, 453-459CrossRef Google Scholar PubMed

107Block, M.L., Zecca, L. and Hong, J.S. (2007) Microglia-mediated neurotoxicity: uncovering the molecular mechanisms. Nature Reviews Neuroscience 8, 57-69CrossRef Google Scholar PubMed

108Hashimoto, M. et al. (2005) Inflammation-induced GDNF improves locomotor function after spinal cord injury. Neuroreport 16, 99-102CrossRef Google Scholar PubMed

109Dougherty, K.D., Dreyfus, C.F. and Black, I.B. (2000) Brain-derived neurotrophic factor in astrocytes, oligodendrocytes, and microglia/macrophages after spinal cord injury. Neurobiology of Disease 7, 574-585CrossRef Google Scholar PubMed

110Shechter, R. et al. (2009) Infiltrating blood-derived macrophages are vital cells playing an anti-inflammatory role in recovery from spinal cord injury in mice. PLoS Medicine 6, e1000113CrossRef Google Scholar PubMed

111Rolls, A. et al. (2008) Two faces of chondroitin sulfate proteoglycan in spinal cord repair: a role in microglia/macrophage activation. PLoS Medicine 5, e171CrossRef Google Scholar PubMed

112Raivich, G. et al. (2004) The AP-1 transcription factor c-Jun is required for efficient axonal regeneration. Neuron 43, 57-67CrossRef Google Scholar PubMed

113Skene, J.H. (1989) Axonal growth-associated proteins. Annual Review of Neuroscience 12, 127-156CrossRef Google Scholar PubMed

114Qiu, J. et al. (2005) Conditioning injury-induced spinal axon regeneration requires signal transducer and activator of transcription 3 activation. Journal of Neuroscience 25, 1645-1653CrossRef Google Scholar PubMed

115Rossi, F., Buffo, A. and Strata, P. (2001) Regulation of intrinsic regenerative properties and axonal plasticity in cerebellar Purkinje cells. Restor Neurol Neurosci 19, 85-94Google Scholar PubMed

116Ziv, N.E. and Spira, M.E. (1997) Localized and transient elevations of intracellular Ca2+ induce the dedifferentiation of axonal segments into growth cones. Journal of Neuroscience 17, 3568-3579CrossRef Google Scholar PubMed

117Chierzi, S. et al. (2005) The ability of axons to regenerate their growth cones depends on axonal type and age, and is regulated by calcium, cAMP and ERK. European Journal of Neuroscience 21, 2051-2062CrossRef Google Scholar PubMed

118Xie, X.Y. and Barrett, J.N. (1991) Membrane resealing in cultured rat septal neurons after neurite transection: evidence for enhancement by Ca(2+)-triggered protease activity and cytoskeletal disassembly. Journal of Neuroscience 11, 3257-3267CrossRef Google Scholar PubMed

119Yoo, S. et al. (2003) Plasmalemmal sealing of transected mammalian neurites is a gradual process mediated by Ca(2+)-regulated proteins. Journal of Neuroscience Research 74, 541-551CrossRef Google Scholar PubMed

120Spira, M.E. et al. (2003) Critical calpain-dependent ultrastructural alterations underlie the transformation of an axonal segment into a growth cone after axotomy of cultured Aplysia neurons. Journal of Comparative Neurology 457, 293-312CrossRef Google Scholar PubMed

121Chu, G.K. and Tator, C.H. (2001) Calcium influx is necessary for optimal regrowth of transected neurites of rat sympathetic ganglion neurons in vitro. Neuroscience 102, 945-957CrossRef Google Scholar PubMed

122Gitler, D. and Spira, M.E. (1998) Real time imaging of calcium-induced localized proteolytic activity after axotomy and its relation to growth cone formation. Neuron 20, 1123-1135CrossRef Google Scholar PubMed

123Cai, D. et al. (1999) Prior exposure to neurotrophins blocks inhibition of axonal regeneration by MAG and myelin via a cAMP-dependent mechanism. Neuron 22, 89-101CrossRef Google Scholar

124Li, Y. et al. (2003) Axon regeneration in goldfish and rat retinal ganglion cells: differential responsiveness to carbohydrates and cAMP. Journal of Neuroscience 23, 7830-7838CrossRef Google Scholar PubMed

125Qiu, J. et al. (2002) Spinal axon regeneration induced by elevation of cyclic AMP. Neuron 34, 895-903CrossRef Google Scholar PubMed

126Qiu, J., Cai, D. and Filbin, M.T. (2002) A role for cAMP in regeneration during development and after injury. Progress in Brain Research 137, 381-387CrossRef Google Scholar PubMed

127Meyer-Franke, A. et al. (1998) Depolarization and cAMP elevation rapidly recruit TrkB to the plasma membrane of CNS neurons. Neuron 21, 681-693CrossRef Google Scholar

128Gao, Y. et al. (2003) Neurotrophins elevate cAMP to reach a threshold required to overcome inhibition by MAG through extracellular signal-regulated kinase-dependent inhibition of phosphodiesterase. Journal of Neuroscience 23, 11770-11777CrossRef Google Scholar

129Lange, P.S. et al. (2004) Novel roles for arginase in cell survival, regeneration, and translation in the central nervous system. Journal of Nutrition 134, 2812S-2817SCrossRef Google Scholar PubMed

130Neumann, S. and Woolf, C.J. (1999) Regeneration of dorsal column fibers into and beyond the lesion site following adult spinal cord injury. Neuron 23, 83-91CrossRef Google Scholar PubMed

131Cai, D. et al. (2002) Arginase I and polyamines act downstream from cyclic AMP in overcoming inhibition of axonal growth MAG and myelin in vitro. Neuron 35, 711-719CrossRef Google Scholar PubMed

132Cao, Z. et al. (2006) The cytokine interleukin-6 is sufficient but not necessary to mimic the peripheral conditioning lesion effect on axonal growth. Journal of Neuroscience 26, 5565-5573CrossRef Google Scholar

133Domowicz, M.S. et al. (2008) Aggrecan is expressed by embryonic brain glia and regulates astrocyte development. Developmental Biology 315, 114-124CrossRef Google Scholar PubMed

134Schreyer, D.J. and Skene, J.H. (1993) Injury-associated induction of GAP-43 expression displays axon branch specificity in rat dorsal root ganglion neurons. Journal of Neurobiology 24, 959-970CrossRef Google Scholar PubMed

135Seijffers, R., Allchorne, A.J. and Woolf, C.J. (2006) The transcription factor ATF-3 promotes neurite outgrowth. Molecular and Cellular Neurosciences 32, 143-154CrossRef Google Scholar PubMed

136Atwal, J.K. et al. (2000) The TrkB-Shc site signals neuronal survival and local axon growth via MEK and P13-kinase. Neuron 27, 265-277CrossRef Google Scholar PubMed

137Liu, R.Y. and Snider, W.D. (2001) Different signaling pathways mediate regenerative versus developmental sensory axon growth. Journal of Neuroscience 21, RC164CrossRef Google Scholar PubMed

138Markus, A., Zhong, J. and Snider, W.D. (2002) Raf and akt mediate distinct aspects of sensory axon growth. Neuron 35, 65-76CrossRef Google Scholar PubMed

139Gallo, G. and Letourneau, P.C. (1998) Localized sources of neurotrophins initiate axon collateral sprouting. Journal of Neuroscience 18, 5403-5414CrossRef Google Scholar PubMed

140Gadient, R.A. and Otten, U.H. (1997) Interleukin-6 (IL-6)–a molecule with both beneficial and destructive potentials. Progress in Neurobiology 52, 379-390CrossRef Google Scholar PubMed

141Ishizaki, T. et al. (2000) Pharmacological properties of Y-27632, a specific inhibitor of rho-associated kinases. Molecular Pharmacology 57, 976-983Google Scholar PubMed

142Dergham, P. et al. (2002) Rho signaling pathway targeted to promote spinal cord repair. Journal of Neuroscience 22, 6570-6577CrossRef Google Scholar PubMed

143Monnier, P.P. et al. (2003) The Rho/ROCK pathway mediates neurite growth-inhibitory activity associated with the chondroitin sulfate proteoglycans of the CNS glial scar. Molecular and Cellular Neurosciences 22, 319-330CrossRef Google Scholar PubMed

144Borisoff, J.F. et al. (2003) Suppression of Rho-kinase activity promotes axonal growth on inhibitory CNS substrates. Molecular and Cellular Neurosciences 22, 405-416CrossRef Google Scholar PubMed

145Chan, C.C. et al. (2005) Dose-dependent beneficial and detrimental effects of ROCK inhibitor Y27632 on axonal sprouting and functional recovery after rat spinal cord injury. Experimental Neurology 196, 352-364CrossRef Google Scholar PubMed

146Fournier, A.E., Takizawa, B.T. and Strittmatter, S.M. (2003) Rho kinase inhibition enhances axonal regeneration in the injured CNS. Journal of Neuroscience 23, 1416-1423CrossRef Google Scholar PubMed

147Wahl, S. et al. (2000) Ephrin-A5 induces collapse of growth cones by activating Rho and Rho kinase. Journal of Cell Biology 149, 263-270CrossRef Google Scholar PubMed

148Sjoberg, J. and Kanje, M. (1990) Effects of repetitive conditioning crush lesions on regeneration of the rat sciatic nerve. Brain Research 530, 167-169CrossRef Google Scholar PubMed

149Gaete, J., Kameid, G. and Alvarez, J. (1998) Regenerating axons of the rat require a local source of proteins. Neuroscience Letters 251, 197-200CrossRef Google Scholar PubMed

150Verma, P. et al. (2005) Axonal protein synthesis and degradation are necessary for efficient growth cone regeneration. Journal of Neuroscience 25, 331-342CrossRef Google Scholar PubMed

151Twiss, J.L. and van Minnen, J. (2006) New insights into neuronal regeneration: the role of axonal protein synthesis in pathfinding and axonal extension. Journal of Neurotrauma 23, 295-308CrossRef Google Scholar PubMed

152Zheng, J.Q. et al. (2001) A functional role for intra-axonal protein synthesis during axonal regeneration from adult sensory neurons. Journal of Neuroscience 21, 9291-9303CrossRef Google Scholar PubMed

153Hanz, S. et al. (2003) Axoplasmic importins enable retrograde injury signaling in lesioned nerve. Neuron 40, 1095-1104CrossRef Google Scholar PubMed

154Guirland, C. et al. (2004) Lipid rafts mediate chemotropic guidance of nerve growth cones. Neuron 42, 51-62CrossRef Google Scholar PubMed

155Ledeen, R.W. et al. (1998) The role of GM1 and other gangliosides in neuronal differentiation. Overview and new finding. Annals of the New York Academy of Sciences 845, 161-175CrossRef Google Scholar PubMed

156Harel, R. and Futerman, A.H. (1993) Inhibition of sphingolipid synthesis affects axonal outgrowth in cultured hippocampal neurons. Journal of Biological Chemistry 268, 14476-14481CrossRef Google Scholar PubMed

157Vyas, A.A. et al. (2002) Gangliosides are functional nerve cell ligands for myelin-associated glycoprotein (MAG), an inhibitor of nerve regeneration. Proceedings of the National Academy of Sciences of the United States of America 99, 8412-8417CrossRef Google Scholar PubMed

158Yang, L.J. et al. (2006) Sialidase enhances spinal axon outgrowth in vivo. Proceedings of the National Academy of Sciences of the United States of America 103, 11057-11062CrossRef Google Scholar PubMed

159Wu, G., Nakamura, K. and Ledeen, R.W. (1994) Inhibition of neurite outgrowth of neuroblastoma Neuro-2a cells by cholera toxin B-subunit and anti-GM1 antibody. Molecular and Chemical Neuropathology 21, 259-271CrossRef Google Scholar PubMed

160Spirman, N. et al. (1984) Regenerative capacity of the goldfish visual system is affected by antibodies specific to gangliosides injected intraocularly. Journal of Neuroimmunology 6, 197-207CrossRef Google Scholar PubMed

161Ferrari, G. et al. (1995) Prevention of apoptotic neuronal death by GM1 ganglioside. Involvement of Trk neurotrophin receptors. Journal of Biological Chemistry 270, 3074-3080CrossRef Google Scholar PubMed

162Rybak, S., Ginzburg, I. and Yavin, E. (1983) Gangliosides stimulate neurite outgrowth and induce tubulin mRNA accumulation in neural cells. Biochemical and Biophysical Research Communications 116, 974-980CrossRef Google Scholar PubMed

163Schneider, J.S., Schroeder, J.A. and Rothblat, D.S. (1998) Differential recovery of sensorimotor function in GM1 ganglioside-treated vs. spontaneously recovered MPTP-treated cats: partial striatal dopaminergic reinnervation vs. neurochemical compensation. Brain Research 813, 82-87CrossRef Google Scholar PubMed

164Geisler, F.H. et al. (2001) The Sygen multicenter acute spinal cord injury study. Spine 26, S87-98CrossRef Google Scholar PubMed

165Riboni, L. et al. (1990) Patterns of endogenous gangliosides and metabolic processing of exogenous gangliosides in cerebellar granule cells during differentiation in culture. Neurochemical Research 15, 1175-1183CrossRef Google Scholar PubMed

166Neugebauer, K.M. and Reichardt, L.F. (1991) Cell-surface regulation of beta 1-integrin activity on developing retinal neurons. Nature 350, 68-71CrossRef Google Scholar PubMed

167Lemons, M.L. and Condic, M.L. (2006) Combined integrin activation and intracellular cAMP cause Rho GTPase dependent growth cone collapse on laminin-1. Experimental Neurology 202, 324-335CrossRef Google Scholar PubMed

168Yanagida, H., Tanaka, J. and Maruo, S. (1999) Immunocytochemical localization of a cell adhesion molecule, integrin alpha5beta1, in nerve growth cones. Journal of Orthopaedic Science 4, 353-360CrossRef Google Scholar PubMed

169Wallquist, W. et al. (2004) Dorsal root ganglion neurons up-regulate the expression of laminin-associated integrins after peripheral but not central axotomy. Journal of Comparative Neurology 480, 162-169CrossRef Google Scholar

170Gardiner, N.J. et al. (2005) Alpha7 integrin mediates neurite outgrowth of distinct populations of adult sensory neurons. Molecular and Cellular Neurosciences 28, 229-240CrossRef Google Scholar PubMed

171Ekstrom, P.A. et al. (2003) Involvement of alpha7beta1 integrin in the conditioning-lesion effect on sensory axon regeneration. Molecular and Cellular Neurosciences 22, 383-395CrossRef Google Scholar PubMed

172Plantman, S. et al. (2005) Integrin messenger RNAs in the red nucleus after axotomy and neurotrophic administration. Neuroreport 16, 709-713CrossRef Google Scholar PubMed

173Andrews, M.R. et al. (2009) Alpha9 integrin promotes neurite outgrowth on tenascin-C and enhances sensory axon regeneration. Journal of Neuroscience 29, 5546-5557CrossRef Google Scholar PubMed

Article contents

Extrinsic and intrinsic factors controlling axonal regeneration after spinal cord injury

Abstract

Access options

References

References

Further reading, resources and contacts

This article has been cited by the following publications. This list is generated based on data provided by Crossref.

Article contents

Extrinsic and intrinsic factors controlling axonal regeneration after spinal cord injury

Abstract

Access options

References

References

Further reading, resources and contacts

Save article to Kindle

Save article to Dropbox

Save article to Google Drive

Reply to: Submit a response

Your details

You have entered the maximum number of contributors

Conflicting interests