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The Involvement of the Myelin-Associated Inhibitors and Their Receptors in CNS Plasticity and Injury

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Abstract

The limited capacity for the central nervous system (CNS) to repair itself was first described over 100 years ago by Spanish neuroscientist Ramon Y. Cajal. However, the exact mechanisms underlying this failure in neuronal regeneration remain unclear and, as such, no effective therapeutics yet exist. Numerous studies have attempted to elucidate the biochemical and molecular mechanisms that inhibit neuronal repair with increasing evidence suggesting that several inhibitory factors and repulsive guidance cues active during development actually persist into adulthood and may be contributing to the inhibition of repair. For example, in the injured adult CNS, there are various inhibitory factors that impede the outgrowth of neurites from damaged neurons. One of the most potent of these neurite outgrowth inhibitors is the group of proteins known as the myelin-associated inhibitors (MAIs), present mainly on the membranes of oligodendroglia. Several studies have shown that interfering with these proteins can have positive outcomes in CNS injury models by promoting neurite outgrowth and improving functional recovery. As such, the MAIs, their receptors, and downstream effectors are valid drug targets for the treatment of CNS injury. This review will discuss the current literature on MAIs in the context of CNS development, plasticity, and injury. Molecules that interfere with the MAIs and their receptors as potential candidates for the treatment of CNS injury will additionally be introduced in the context of preclinical and clinical trials.

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References

  1. Nave KA, Werner HB (2014) Myelination of the nervous system: mechanisms and functions. Annu Rev Cell Dev Biol 30:503–533. doi:10.1146/annurev-cellbio-100913-013101

    Article  CAS  PubMed  Google Scholar 

  2. Quarles RH, Macklin WB, Morell P (2006) Myelin formation, structure and biochemistry. In: Siegel GJ, Agranoff BW, Albers RW, Brady ST, Price DL (eds) Basic neurochemistry: molecular, cellular and medical aspects, 7th edn. Academic Press, Elsevier, San Diego, pp. 51–71

    Google Scholar 

  3. Bock NA, Kocharyan A, Liu JV, Silva AC (2009) Visualizing the entire cortical myelination pattern in marmosets with magnetic resonance imaging. J Neurosci Methods 185:15–22. doi:10.1016/j.jneumeth.2009.08.022

    Article  PubMed  PubMed Central  Google Scholar 

  4. Aubert-Broche B, Fonov V, Leppert I, Pike GB, Collins DL (2008) Human brain myelination from birth to 4.5 years. Med Image Comput Comput Assist Interv 11:180–187

    CAS  PubMed  Google Scholar 

  5. Deoni SC, Mercure E, Blasi A, Gasston D, Thomson A, Johnson M, Williams SC, Murphy DG (2011) Mapping infant brain myelination with magnetic resonance imaging. J Neurosci 31:784–791. doi:10.1523/JNEUROSCI.2106-10.2011

    Article  CAS  PubMed  Google Scholar 

  6. Gogtay N, Giedd JN, Lusk L, Hayashi KM, Greenstein D, Vaituzis AC, Nugent TF, Herman DH et al (2004) Dynamic mapping of human cortical development during childhood through early adulthood. Proc Natl Acad Sci U S A 101:8174–8179. doi:10.1073/pnas.0402680101

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Semple BD, Blomgren K, Gimlin K, Ferriero DM, Noble-Haeusslein LJ (2013) Brain development in rodents and humans: identifying benchmarks of maturation and vulnerability to injury across species. Prog Neurobiol 0:1–16. doi:10.1016/j.pneurobio.2013.04.001

    Article  PubMed Central  Google Scholar 

  8. Flechsig P (1920) Anatomie des menschlichen Gehirns und Rückenmarks auf myelogenetischer Grundlage. Thieme, Leipzig

    Google Scholar 

  9. Finger S, Wolf C (1988) The ‘Kennard effect’ before Kennard. The early history of age and brain lesions. Arch Neurol 45:1136–1142

    Article  CAS  PubMed  Google Scholar 

  10. Schwab ME, Caroni P (1988) Oligodendrocytes and CNS myelin are nonpermissive substrates for neurite growth and fibroblast spreading in vitro. J Neurosci 8:2381–2393

    CAS  PubMed  Google Scholar 

  11. Caroni P, Schwab ME (1988) Antibody against myelin-associated inhibitor of neurite growth neutralizes nonpermissive substrate properties of CNS white matter. Neuron 1:85–96

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  13. Atwal JK, Pinkston-Gosse J, Syken J, Stawicki S, Wu Y, Shatz C, Tessier-Lavigne M (2008) PirB is a functional receptor for myelin inhibitors of axonal regeneration. Science 322:967–970

    Article  CAS  PubMed  Google Scholar 

  14. Domeniconi M, Cao Z, Spencer T, Sivasankaran R, Wang KC, Nikulina E, Kimura N, Cai H et al (2002) Myelin-associated glycoprotein interacts with the Nogo66 receptor to inhibit neurite outgrowth. Neuron 35:283–290

    Article  CAS  PubMed  Google Scholar 

  15. Fournier AE, GrandPre T, Strittmatter SM (2001) Identification of a receptor mediating nogo-66 inhibition of axonal regeneration. Nature 409:341–346

    Article  CAS  PubMed  Google Scholar 

  16. Wang KC, Koprivica V, Kim JA, Sivasankaran R, Guo Y, Neve RL, He Z (2002) Oligodendrocyte-myelin glycoprotein is a nogo receptor ligand that inhibits neurite outgrowth. Nature 417:941–944

    Article  CAS  PubMed  Google Scholar 

  17. Venkatesh K, Chivatakarn O, Lee H, Joshi PS, Kantor DB, Newman BA, Mage R, Rader C et al (2005) The nogo-66 receptor homolog NgR2 is a sialic acid-dependent receptor selective for myelin-associated glycoprotein. J Neurosci 25:808–822. doi:10.1523/JNEUROSCI.4464-04.2005

    Article  CAS  PubMed  Google Scholar 

  18. Chen MS, Huber AB, Van Der Haar MED, Frank M, Schnell L, Spillmann AA, Christ F, Schwab ME (2000) Nogo-a is a myelin-associated neurite outgrowth inhibitor and an antigen for monoclonal antibody IN-1. Nature 403:434–439

    Article  CAS  PubMed  Google Scholar 

  19. GrandPré T, Nakamura F, Vartanlan T, Strittmatter SM (2000) Identification of the nogo inhibitor of axon regeneration as a reticulon protein. Nature 403:439–444

    Article  PubMed  Google Scholar 

  20. Laurén J, Hu F, Chin J, Liao J, Airaksinen MS, Strittmatter SM (2007) Characterization of myelin ligand complexes with neuronal nogo-66 receptor family members. J Biol Chem 282:5715–5725. doi:10.1074/jbc.M609797200

    Article  PubMed  Google Scholar 

  21. Hu F, Liu BP, Budel S, Liao J, Chin J, Fournier A, Strittmatter SM (2005) Nogo-a interacts with the nogo-66 receptor through multiple sites to create an isoform-selective subnanomolar agonist. J Neurosci 25:5298–5304. doi:10.1523/JNEUROSCI.5235-04.2005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Kempf A, Tews B, Arzt ME, Weinmann O, Obermair FJ, Pernet V, Zagrebelsky M, Delekate A et al (2014) The sphingolipid receptor S1PR2 is a receptor for nogo-a repressing synaptic plasticity. PLoS Biol 12:e1001763

    Article  PubMed  PubMed Central  Google Scholar 

  23. Oertle T, van der Haar ME, Bandtlow CE, Robeva A, Burfeind P, Buss A, Huber AB, Simonen M et al (2003) Nogo-a inhibits neurite outgrowth and cell spreading with three discrete regions. J Neurosci 23:5393–5406

    CAS  PubMed  Google Scholar 

  24. Huebner EA, Kim BG, Duffy PJ, Brown RH, Strittmatter SM (2011) A multi-domain fragment of nogo-a protein is a potent inhibitor of cortical axon regeneration via nogo receptor 1. J Biol Chem 286:18026–18036. doi:10.1074/jbc.M110.208108

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Dodd DA, Niederoest B, Bloechlinger S, Dupuis L, Loeffler JP, Schwab ME (2005) Nogo-A, -B, and -C are found on the cell surface and interact together in many different cell types. J Biol Chem 280:12494–12502. doi:10.1074/jbc.M411827200

    Article  CAS  PubMed  Google Scholar 

  26. Prinjha R, Moore SE, Vinson M, Blake S, Morrow R, Christie G, Michalovich D, Simmons DL et al (2000) Inhibitor of neurite outgrowth in humans. Nature 403:383–384

    Article  CAS  PubMed  Google Scholar 

  27. Yang YS, Strittmatter SM (2007) The reticulons: a family of proteins with diverse functions. Genome Biol 8:234. doi:10.1186/gb-2007-8-12-234

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  28. Cafferty WB, Duffy P, Huebner E, Strittmatter SM (2010) MAG and OMgp synergize with nogo-A to restrict axonal growth and neurological recovery after spinal cord trauma. J Neurosci 30:6825–6837. doi:10.1523/JNEUROSCI.6239-09.2010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Huber AB, Weinmann O, Brösamle C, Oertle T, Schwab ME (2002) Patterns of nogo mRNA and protein expression in the developing and adult rat and after CNS lesions. J Neurosci 22:3553–3567

    CAS  PubMed  Google Scholar 

  30. Hunt D, Coffin RS, Prinjha RK, Campbell G, Anderson PN (2003) Nogo-A expression in the intact and injured nervous system. Mol Cell Neurosci 24:1083–1102

    Article  CAS  PubMed  Google Scholar 

  31. Meier S, Brauer AU, Heimrich B, Schwab ME, Nitsch R, Savaskan NE (2003) Molecular analysis of nogo expression in the hippocampus during development and following lesion and seizure. FASEB J 17:1153–1155. doi:10.1096/fj.02-0453fje

    Article  CAS  PubMed  Google Scholar 

  32. Mingorance A, Fontana X, Sole M, Burgaya F, Urena JM, Teng FY, Tang BL, Hunt D et al (2004) Regulation of nogo and nogo receptor during the development of the entorhino-hippocampal pathway and after adult hippocampal lesions. Mol Cell Neurosci 26:34–49. doi:10.1016/j.mcn.2004.01.001

    Article  CAS  PubMed  Google Scholar 

  33. Richard M, Giannetti N, Saucier D, Sacquet J, Jourdan F, Pellier-Monnin V (2005) Neuronal expression of nogo-A mRNA and protein during neurite outgrowth in the developing rat olfactory system. Eur J Neurosci 22:2145–2158. doi:10.1111/j.1460-9568.2005.04418.x

    Article  PubMed  Google Scholar 

  34. Lee H, Raiker SJ, Venkatesh K, Geary R, Robak LA, Zhang Y, Yeh HH, Shrager P et al (2008) Synaptic function for the nogo-66 receptor NgR1: regulation of dendritic spine morphology and activity-dependent synaptic strength. J Neurosci 28:2753–2765. doi:10.1523/JNEUROSCI.5586-07.2008

    Article  CAS  PubMed  Google Scholar 

  35. Liu YY, Jin WL, Liu HL, Ju G (2003) Electron microscopic localization of Nogo-A at the postsynaptic active zone of the rat. Neurosci Lett 346:153–156

    Article  CAS  PubMed  Google Scholar 

  36. Wang X, Chun SJ, Treloar H, Vartanian T, Greer CA, Strittmatter SM (2002) Localization of Nogo-A and Nogo-66 receptor proteins at sites of axon-myelin and synaptic contact. J Neurosci 22:5505–5515

    CAS  PubMed  Google Scholar 

  37. Voeltz GK, Prinz WA, Shibata Y, Rist JM, Rapoport TA (2006) A class of membrane proteins shaping the tubular endoplasmic reticulum. Cell 124:573–586. doi:10.1016/j.cell.2005.11.047

    Article  CAS  PubMed  Google Scholar 

  38. Acevedo L, Yu J, Erdjument-Bromage H, Miao RQ, Kim JE, Fulton D, Tempst P, Strittmatter SM et al (2004) A new role for nogo as a regulator of vascular remodeling. Nat Med 10:382–388. doi:10.1038/nm1020

    Article  CAS  PubMed  Google Scholar 

  39. Schwab ME (2010) Functions of nogo proteins and their receptors in the nervous system. Nat Rev Neurosci 11:799–811

    Article  CAS  PubMed  Google Scholar 

  40. Salzer JL, Holmes WP, Colman DR (1987) The amino acid sequences of the myelin-associated glycoproteins: homology to the immunoglobulin gene superfamily. J Cell Biol 104:957–965

    Article  CAS  PubMed  Google Scholar 

  41. Miescher GC, Lutzelschwab R, Erne B, Ferracin F, Huber S, Steck AJ (1997) Reciprocal expression of myelin-associated glycoprotein splice variants in the adult human peripheral and central nervous systems. Mol Brain Res 52:299–306. doi:10.1016/S0169-328x(97)00254-4

    Article  CAS  PubMed  Google Scholar 

  42. Fujita N, Kemper A, Dupree J, Nakayasu H, Bartsch U, Schachner M, Maeda N, Suzuki K et al (1998) The cytoplasmic domain of the large myelin-associated glycoprotein isoform is needed for proper CNS but not peripheral nervous system myelination. J Neurosci 18:1970–1978

    CAS  PubMed  Google Scholar 

  43. Sternberger NH, Quarles RH, Itoyama Y, Webster HD (1979) Myelin-associated glycoprotein demonstrated immunocytochemically in myelin and myelin-forming cells of developing rat. Proc Natl Acad Sci U S A 76:1510–1514

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Johnson PW, Abramow-Newerly W, Seilheimer B, Sadoul R, Tropak MB, Arquint M, Dunn RJ, Schachner M et al (1989) Recombinant myelin-associated glycoprotein confers neural adhesion and neurite outgrowth function. Neuron 3:377–385

    Article  CAS  PubMed  Google Scholar 

  45. Turnley AM, Bartlett PF (1998) MAG and MOG enhance neurite outgrowth of embryonic mouse spinal cord neurons. Neuroreport 9:1987–1990

    Article  CAS  PubMed  Google Scholar 

  46. McKerracher L, David S, Jackson DL, Kottis V, Dunn RJ, Braun PE (1994) Identification of myelin-associated glycoprotein as a major myelin-derived inhibitor of neurite growth. Neuron 13:805–811

    Article  CAS  PubMed  Google Scholar 

  47. Mukhopadhyay G, Doherty P, Walsh FS, Crocker PR, Filbin MT (1994) A novel role for myelin-associated glycoprotein as an inhibitor of axonal regeneration. Neuron 13:757–767

    Article  CAS  PubMed  Google Scholar 

  48. Shen YJ, DeBellard ME, Salzer JL, Roder J, Filbin MT (1998) Myelin-associated glycoprotein in myelin and expressed by Schwann cells inhibits axonal regeneration and branching. Mol Cell Neurosci 12:79–91. doi:10.1006/mcne.1998.0700

    Article  CAS  PubMed  Google Scholar 

  49. Thiede-Stan NK, Schwab ME (2015) Attractive and repulsive factors act through multi-subunit receptor complexes to regulate nerve fiber growth. J Cell Sci 128:2403–2414. doi:10.1242/jcs.165555

    Article  CAS  PubMed  Google Scholar 

  50. Schnaar RL (2010) Brain gangliosides in axon–myelin stability and axon regeneration. FEBS Lett 584:1741–1747. doi:10.1016/j.febslet.2009.10.011

    Article  CAS  PubMed  Google Scholar 

  51. Mikol DD, Gulcher JR, Stefansson K (1990) The oligodendrocyte-myelin glycoprotein belongs to a distinct family of proteins and contains the HNK-1 carbohydrate. J Cell Biol 110:471–479

    Article  CAS  PubMed  Google Scholar 

  52. Mikol DD, Rongnoparut P, Allwardt BA, Marton LS, Stefansson K (1993) The oligodendrocyte myelin glycoprotein of mouse—primary structure and gene structure. Genomics 17:604–610. doi:10.1006/Geno.1993.1379

    Article  CAS  PubMed  Google Scholar 

  53. Mikol DD, Stefansson K (1988) A phosphatidylinositol-linked peanut agglutinin-binding glycoprotein in central nervous system myelin and on oligodendrocytes. J Cell Biol 106:1273–1279

    Article  CAS  PubMed  Google Scholar 

  54. Habib AA, Marton LS, Allwardt B, Gulcher JR, Mikol DD, Hognason T, Chattopadhyay N, Stefansson K (1998) Expression of the oligodendrocyte-myelin glycoprotein by neurons in the mouse central nervous system. J Neurochem 70:1704–1711

    Article  CAS  PubMed  Google Scholar 

  55. Kottis V, Thibault P, Mikol D, Xiao ZC, Zhang R, Dergham P, Braun PE (2002) Oligodendrocyte-myelin glycoprotein (OMgp) is an inhibitor of neurite outgrowth. J Neurochem 82:1566–1569

    Article  CAS  PubMed  Google Scholar 

  56. Llorens F, Gil V, Del Río JA (2011) Emerging functions of myelin-associated proteins during development, neuronal plasticity, and neurodegeneration. FASEB J 25:463–475

    Article  CAS  PubMed  Google Scholar 

  57. Huang JK, Phillips GR, Roth AD, Pedraza L, Shan WS, Belkaid W, Mi S, Fex-Svenningsen A et al (2005) Glial membranes at the node of Ranvier prevent neurite outgrowth. Science 310:1813–1817. doi:10.1126/Science.1118313

    Article  CAS  PubMed  Google Scholar 

  58. Josephson A, Trifunovski A, Widmer HR, Widenfalk J, Olson L, Spenger C (2002) Nogo-receptor gene activity: cellular localization and developmental regulation of mRNA in mice and humans. J Comp Neurol 453:292–304

    Article  CAS  PubMed  Google Scholar 

  59. Chivatakarn O, Kaneko S, He Z, Tessier-Lavigne M, Giger RJ (2007) The nogo-66 receptor NgR1 is required only for the acute growth cone-collapsing but not the chronic growth-inhibitory actions of myelin inhibitors. J Neurosci 27:7117–7124

    Article  CAS  PubMed  Google Scholar 

  60. Barton WA, Liu BP, Tzvetkova D, Jeffrey PD, Fournier AE, Sah D, Cate R, Strittmatter SM et al (2003) Structure and axon outgrowth inhibitor binding of the nogo-66 receptor and related proteins. EMBO J 22:3291–3302. doi:10.1093/emboj/cdg325

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Park JB, Yiu G, Kaneko S, Wang J, Chang J, He XL, Garcia KC, He Z (2005) A TNF receptor family member, TROY, is a coreceptor with nogo receptor in mediating the inhibitory activity of myelin inhibitors. Neuron 45:345–351. doi:10.1016/j.neuron.2004.12.040

    Article  CAS  PubMed  Google Scholar 

  62. Shao Z, Browning JL, Lee X, Scott ML, Shulga-Morskaya S, Allaire N, Thill G, Levesque M et al (2005) TAJ/TROY, an orphan TNF receptor family member, binds nogo-66 receptor 1 and regulates axonal regeneration. Neuron 45:353–359

    Article  CAS  PubMed  Google Scholar 

  63. Wang KC, Kim JA, Sivasankaran R, Segal R, He Z (2002) p75 interacts with the nogo receptor as a co-receptor for nogo, MAG and OMgp. Nature 420:74–78

    Article  CAS  PubMed  Google Scholar 

  64. Wong ST, Henley JR, Kanning KC, Huang KH, Bothwell M, Poo MM (2002) A p75(NTR) and nogo receptor complex mediates repulsive signaling by myelin-associated glycoprotein. Nat Neurosci 5:1302–1308. doi:10.1038/nn975

    Article  CAS  PubMed  Google Scholar 

  65. Mi S, Miller RH, Lee X, Scott ML, Shulag-Morskaya S, Shao Z, Chang J, Thill G et al (2005) LINGO-1 negatively regulates myelination by oligodendrocytes. Nat Neurosci 8:745–751. doi:10.1038/nn1460

    Article  CAS  PubMed  Google Scholar 

  66. Mi S, Lee X, Shao Z, Thill G, Ji B, Relton J, Levesque M, Allaire N et al (2004) LINGO-1 is a component of the nogo-66 receptor/p75 signaling complex. Nat Neurosci 7:221–228

    Article  CAS  PubMed  Google Scholar 

  67. Fujitani M, Kawai H, Proia RL, Kashiwagi A, Yasuda H, Yamashita T (2005) Binding of soluble myelin-associated glycoprotein to specific gangliosides induces the association of p75NTR to lipid rafts and signal transduction. J Neurochem 94:15–21. doi:10.1111/j.1471-4159.2005.03121.x

    Article  CAS  PubMed  Google Scholar 

  68. Saha N, Kolev MV, Semavina M, Himanen J, Nikolov DB (2011) Ganglioside mediate the interaction between nogo receptor 1 and LINGO-1. Biochem Biophys Res Commun 413:92–97. doi:10.1016/j.bbrc.2011.08.060

    Article  CAS  PubMed  Google Scholar 

  69. Averill S, McMahon SB, Clary DO, Reichardt LF, Priestley JV (1995) Immunocytochemical localization of trkA receptors in chemically identified subgroups of adult rat sensory neurons. Eur J Neurosci 7:1484–1494

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. McMahon SB, Armanini MP, Ling LH, Phillips HS (1994) Expression and coexpression of Trk receptors in subpopulations of adult primary sensory neurons projecting to identified peripheral targets. Neuron 12:1161–1171

    Article  CAS  PubMed  Google Scholar 

  71. Wright DE, Snider WD (1995) Neurotrophin receptor mRNA expression defines distinct populations of neurons in rat dorsal root ganglia. J Comp Neurol 351:329–338. doi:10.1002/cne.903510302

    Article  CAS  PubMed  Google Scholar 

  72. Song XY, Zhong JH, Wang X, Zhou XF (2004) Suppression of p75NTR does not promote regeneration of injured spinal cord in mice. J Neurosci 24:542–546. doi:10.1523/jneurosci.4281-03.2004

    Article  CAS  PubMed  Google Scholar 

  73. Kojima T, Morikawa Y, Copeland NG, Gilbert DJ, Jenkins NA, Senba E, Kitamura T (2000) TROY, a newly identified member of the tumor necrosis factor receptor superfamily, exhibits a homology with Edar and is expressed in embryonic skin and hair follicles. J Biol Chem 275:20742–20747. doi:10.1074/jbc.M002691200

    Article  CAS  PubMed  Google Scholar 

  74. Saha N, Kolev M, Nikolov DB (2014) Structural features of the nogo receptor signaling complexes at the neuron/myelin interface. Neurosci Res 87:1–7. doi:10.1016/j.neures.2014.06.003

    Article  CAS  PubMed  Google Scholar 

  75. Timms JF, Carlberg K, Gu H, Chen H, Kamatkar S, Nadler MJ, Rohrschneider LR, Neel BG (1998) Identification of major binding proteins and substrates for the SH2-containing protein tyrosine phosphatase SHP-1 in macrophages. Mol Cell Biol 18:3838–3850

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Adelson J, Barreto G, Xu L, Kim T, Brott B, Ouyang YB, Naserke T, Djurisic M et al (2012) Neuroprotection from stroke in the absence of MHCI or PirB. Neuron 73:1100–1107. doi:10.1016/j.neuron.2012.01.020

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Nakamura Y, Fujita Y, Ueno M, Takai T, Yamashita T (2011) Paired immunoglobulin-like receptor B knockout does not enhance axonal regeneration or locomotor recovery after spinal cord injury. J Biol Chem 286:1876–1883. doi:10.1074/jbc.M110.163493

    Article  CAS  PubMed  Google Scholar 

  78. Syken J, Grandpre T, Kanold PO, Shatz CJ (2006) PirB restricts ocular-dominance plasticity in visual cortex. Science 313:1795–1800. doi:10.1126/science.1128232

    Article  CAS  PubMed  Google Scholar 

  79. Fujita Y, Takashima R, Endo S, Takai T, Yamashita T (2011) The p75 receptor mediates axon growth inhibition through an association with PIR-B. Cell Death and Dis 2:e198. doi:10.1038/cddis.2011.85

    Article  CAS  Google Scholar 

  80. Tozaki H, Kawasaki T, Takagi Y, Hirata T (2002) Expression of nogo protein by growing axons in the developing nervous system. Brain Res Mol Brain Res 104:111–119

    Article  CAS  PubMed  Google Scholar 

  81. Mingorance-Le Meur A, Zheng B, Soriano E, del Rio JA (2007) Involvement of the myelin-associated inhibitor nogo-a in early cortical development and neuronal maturation. Cereb Cortex 17:2375–2386. doi:10.1093/cercor/bhl146

    Article  PubMed  Google Scholar 

  82. Wang J, Chan CK, Taylor JS, Chan SO (2008) Localization of nogo and its receptor in the optic pathway of mouse embryos. J Neurosci Res 86:1721–1733. doi:10.1002/jnr.21626

    Article  CAS  PubMed  Google Scholar 

  83. Mathis C, Schroter A, Thallmair M, Schwab ME (2010) Nogo-a regulates neural precursor migration in the embryonic mouse cortex. Cereb Cortex 20:2380–2390. doi:10.1093/cercor/bhp307

    Article  PubMed  PubMed Central  Google Scholar 

  84. Wang J, Chan CK, Taylor JS, Chan SO (2008) The growth-inhibitory protein nogo is involved in midline routing of axons in the mouse optic chiasm. J Neurosci Res 86:2581–2590. doi:10.1002/jnr.21717

    Article  CAS  PubMed  Google Scholar 

  85. Petrinovic MM, Duncan CS, Bourikas D, Weinman O, Montani L, Schroeter A, Maerki D, Sommer L et al (2010) Neuronal nogo-a regulates neurite fasciculation, branching and extension in the developing nervous system. Development 137:2539–2550. doi:10.1242/dev.048371

    Article  CAS  PubMed  Google Scholar 

  86. Pernet V, Joly S, Christ F, Dimou L, Schwab ME (2008) Nogo-a and myelin-associated glycoprotein differently regulate oligodendrocyte maturation and myelin formation. J Neurosci 28:7435–7444. doi:10.1523/JNEUROSCI.0727-08.2008

    Article  CAS  PubMed  Google Scholar 

  87. Gil V, Bichler Z, Lee JK, Seira O, Llorens F, Bribian A, Morales R, Claverol-Tinture E et al (2010) Developmental expression of the oligodendrocyte myelin glycoprotein in the mouse telencephalon. Cereb Cortex 20:1769–1779. doi:10.1093/cercor/bhp246

    Article  PubMed  Google Scholar 

  88. Vourc'h P, Dessay S, Mbarek O, Marouillat Védrine S, Müh JP, Andres C (2003) The oligodendrocyte-myelin glycoprotein gene is highly expressed during the late stages of myelination in the rat central nervous system. Dev Brain Res 144:159–168

    Article  CAS  Google Scholar 

  89. Vourc'h P, Andres C (2004) Oligodendrocyte myelin glycoprotein (OMgp): evolution, structure and function. Brain Res Brain Res Rev 45:115–124. doi:10.1016/j.brainresrev.2004.01.003

    Article  PubMed  CAS  Google Scholar 

  90. Chang KJ, Susuki K, Dours-Zimmermann MT, Zimmermann DR, Rasband MN (2010) Oligodendrocyte myelin glycoprotein does not influence node of ranvier structure or assembly. J Neurosci 30:14476–14481

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Frantz MG, Kast RJ, Dorton HM, Chapman KS, McGee AW (2016) Nogo receptor 1 limits ocular dominance plasticity but not turnover of axonal boutons in a model of amblyopia. Cereb Cortex 26:1975–1985. doi:10.1093/cercor/bhv014

    Article  PubMed  Google Scholar 

  92. McGee AW, Yang Y, Fischer QS, Daw NW, Strittmatter SH (2005) Neuroscience: experience-driven plasticity of visual cortex limited by myelin and nogo receptor. Science 309:2222–2226

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Bochner DN, Sapp RW, Adelson JD, Zhang S, Lee H, Djurisic M, Syken J, Dan Y et al (2014) Blocking PirB up-regulates spines and functional synapses to unlock visual cortical plasticity and facilitate recovery from amblyopia. Sci Transl Med 6:258ra140. doi:10.1126/scitranslmed.3010157

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  94. Raiker SJ, Lee H, Baldwin KT, Duan Y, Shrager P, Giger RJ (2010) Oligodendrocyte-myelin glycoprotein and nogo negatively regulate activity-dependent synaptic plasticity. J Neurosci 30:12432–12445

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Fang Y, Yao L, Li C, Wang J, Wang J, Chen S, Zhou XF, Liao H (2016) The blockage of the nogo/NgR signal pathway in microglia alleviates the formation of Abeta plaques and tau phosphorylation in APP/PS1 transgenic mice. J Neuroinflammation 13:56. doi:10.1186/s12974-016-0522-x

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  96. Guzik-Kornacka A, van der Bourg A, Vajda F, Joly S, Christ F, Schwab ME, Pernet V (2016) Nogo-a deletion increases the plasticity of the optokinetic response and changes retinal projection organization in the adult mouse visual system. Brain Struct Funct 221:317–329. doi:10.1007/s00429-014-0909-3

    Article  CAS  PubMed  Google Scholar 

  97. Zemmar A, Weinmann O, Kellner Y, Yu X, Vicente R, Gullo M, Kasper H, Lussi K et al (2014) Neutralization of nogo-a enhances synaptic plasticity in the rodent motor cortex and improves motor learning in vivo. J Neurosci 34:8685–8698. doi:10.1523/JNEUROSCI.3817-13.2014

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  98. Fujita Y, Yamashita T (2014) Axon growth inhibition by RhoA/ROCK in the central nervous system. Front Neurosci 8:338. doi:10.3389/fnins.2014.00338

    Article  PubMed  PubMed Central  Google Scholar 

  99. Niederost B, Oertle T, Fritsche J, McKinney RA, Bandtlow CE (2002) Nogo-a and myelin-associated glycoprotein mediate neurite growth inhibition by antagonistic regulation of RhoA and Rac1. J Neurosci 22:10368–10376

    CAS  PubMed  Google Scholar 

  100. Yamashita T, Tohyama M (2003) The p75 receptor acts as a displacement factor that releases rho from rho-GDI. Nat Neurosci 6:461–467

    Article  CAS  PubMed  Google Scholar 

  101. Hsieh SHK, Ferraro GB, Fournier AE (2006) Myelin-associated inhibitors regulate cofilin phosphorylation and neuronal inhibition through LIM kinase and slingshot phosphatase. J Neurosci 26:1006–1015

    Article  CAS  PubMed  Google Scholar 

  102. Taylor J, Chung KH, Figueroa C, Zurawski J, Dickson HM, Brace EJ, Avery AW, Turner DL et al (2008) The scaffold protein POSH regulates axon outgrowth. Mol Biol Cell 19:5181–5192. doi:10.1091/mbc.E08-02-0231

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Gou Z, Mi Y, Jiang F, Deng B, Yang J, Gou X (2014) PirB is a novel potential therapeutic target for enhancing axonal regeneration and synaptic plasticity following CNS injury in mammals. J Drug Target 22:365–371. doi:10.3109/1061186X.2013.878939

    Article  CAS  PubMed  Google Scholar 

  104. Fujita Y, Endo S, Takai T, Yamashita T (2011) Myelin suppresses axon regeneration by PIR-B/SHP-mediated inhibition of Trk activity. EMBO J 30:1389–1401. doi:10.1038/emboj.2011.55

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Tagami S, Eguchi Y, Kinoshita M, Takeda M, Tsujimoto Y (2000) A novel protein, RTN-XS, interacts with both Bcl-XL and Bcl-2 on endoplasmic reticulum and reduces their anti-apoptotic activity. Oncogene 19:5736–5746. doi:10.1038/sj.onc.1203948

    Article  CAS  PubMed  Google Scholar 

  106. Karnezis T, Mandemakers W, McQualter JL, Zheng BH, Ho PP, Jordan KA, Murray BM, Barres B et al (2004) The neurite outgrowth inhibitor nogo a is involved in autoimmune-mediated demyelination. Nat Neurosci 7:736–744. doi:10.1038/nn1261

    Article  CAS  PubMed  Google Scholar 

  107. Jokic N, de Aguilar JLG, Pradat PF, Dupuis L, Echaniz-Laguna A, Muller A, Dubourg O, Seilhean D et al (2005) Nogo expression in muscle correlates with amyotrophic lateral sclerosis severity. Ann Neurol 57:553–556. doi:10.1002/ana.20420

    Article  CAS  PubMed  Google Scholar 

  108. Lang BT, Wang J, Filous AR, Au NP, Ma CH, Shen Y (2014) Pleiotropic molecules in axon regeneration and neuroinflammation. Exp Neurol 258:17–23. doi:10.1016/j.expneurol.2014.04.031

    Article  CAS  PubMed  Google Scholar 

  109. Geoffroy CG, Zheng B (2014) Myelin-associated inhibitors in axonal growth after CNS injury. Curr Opin Neurobiol 27:31–38. doi:10.1016/j.conb.2014.02.012

    Article  CAS  PubMed  Google Scholar 

  110. Cordy JM, Hooper NM, Turner AJ (2006) The involvement of lipid rafts in Alzheimer’s disease. Mol Membr Biol 23:111–122. doi:10.1080/09687860500496417

    Article  CAS  PubMed  Google Scholar 

  111. Tang BL, Liou YC (2007) Novel modulators of amyloid-beta precursor protein processing. J Neurochem 100:314–323. doi:10.1111/j.1471-4159.2006.04215.x

    Article  CAS  PubMed  Google Scholar 

  112. Park JH, Gimbel DA, GrandPre T, Lee JK, Kim JE, Li WW, Lee DHS, Strittmatter SM (2006) Alzheimer precursor protein interaction with the nogo-66 receptor reduces amyloid-beta plaque deposition. J Neurosci 26:1386–1395. doi:10.1523/Jneurosci.3291-05.2006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Park JH, Strittmatter SM (2007) Nogo receptor interacts with brain APP and Abeta to reduce pathologic changes in Alzheimer’s transgenic mice. Curr Alzheimer Res 4:568–570

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. del Zoppo GJ, Sharp FR, Heiss WD, Albers GW (2011) Heterogeneity in the penumbra. J Cereb Blood Flow Metab 31:1836–1851. doi:10.1038/jcbfm.2011.93

    Article  PubMed  PubMed Central  Google Scholar 

  115. Eugenin EA, Berman JW (2003) Chemokine-dependent mechanisms of leukocyte trafficking across a model of the blood-brain barrier. Methods 29:351–361

    Article  CAS  PubMed  Google Scholar 

  116. Woodruff TM, Thundyil J, Tang SC, Sobey CG, Taylor SM, Arumugam TV (2011) Pathophysiology, treatment, and animal and cellular models of human ischemic stroke. Mol Neurodegener 6:11. doi:10.1186/1750-1326-6-11

    Article  PubMed  PubMed Central  Google Scholar 

  117. Broughton BR, Reutens DC, Sobey CG (2009) Apoptotic mechanisms after cerebral ischemia. Stroke 40:e331–e339. doi:10.1161/strokeaha.108.531632

    Article  PubMed  Google Scholar 

  118. Kerr JF, Wyllie AH, Currie AR (1972) Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 26:239–257

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Merson TD, Bourne JA (2014) Endogenous neurogenesis following ischaemic brain injury: insights for therapeutic strategies. Int J Biochem Cell Biol 56:4–19. doi:10.1016/j.biocel.2014.08.003

    Article  CAS  PubMed  Google Scholar 

  120. Gelderblom M, Leypoldt F, Steinbach K, Behrens D, Choe CU, Siler DA, Arumugam TV, Orthey E et al (2009) Temporal and spatial dynamics of cerebral immune cell accumulation in stroke. Stroke 40:1849–1857. doi:10.1161/strokeaha.108.534503

    Article  PubMed  Google Scholar 

  121. Jin R, Yang G, Li G (2010) Inflammatory mechanisms in ischemic stroke: role of inflammatory cells. J Leukoc Biol 87:779–789. doi:10.1189/jlb.1109766

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Mergenthaler P, Dirnagl U, Meisel A (2004) Pathophysiology of stroke: lessons from animal models. Metab Brain Dis 19:151–167

    Article  CAS  PubMed  Google Scholar 

  123. Aggarwal A, Aggarwal P, Khatak M, Khatak S (2010) Cerebral ischemic stroke: sequels of cascade. Int J Pharm Bio Sci 1:3

    Google Scholar 

  124. Aronowski J, Strong R, Grotta JC (1997) Reperfusion injury: demonstration of brain damage produced by reperfusion after transient focal ischemia in rats. J Cereb Blood Flow Metab 17:1048–1056

    Article  CAS  PubMed  Google Scholar 

  125. O'Connell KM, Littleton-Kearney MT (2013) The role of free radicals in traumatic brain injury. Biol Res Nurs 15:253–263. doi:10.1177/1099800411431823

    Article  PubMed  CAS  Google Scholar 

  126. Yang Y, Rosenberg GA (2011) Blood-brain barrier breakdown in acute and chronic cerebrovascular disease. Stroke 42:3323–3328. doi:10.1161/STROKEAHA.110.608257

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Almad A, Sahinkaya FR, McTigue DM (2011) Oligodendrocyte fate after spinal cord injury. Neurotherapeutics 8:262–273. doi:10.1007/s13311-011-0033-5

    Article  PubMed  PubMed Central  Google Scholar 

  128. Goldshmit Y, Bourne J (2010) Upregulation of EphA4 on astrocytes potentially mediates astrocytic gliosis after cortical lesion in the marmoset monkey. J Neurotrauma 27:1321–1332. doi:10.1089/neu.2010.1294

    Article  PubMed  Google Scholar 

  129. Sun F, Lin CL, McTigue D, Shan X, Tovar CA, Bresnahan JC, Beattie MS (2010) Effects of axon degeneration on oligodendrocyte lineage cells: dorsal rhizotomy evokes a repair response while axon degeneration rostral to spinal contusion induces both repair and apoptosis. Glia 58:1304–1319. doi:10.1002/glia.21009

    PubMed  PubMed Central  Google Scholar 

  130. Wang JT, Medress ZA, Barres BA (2012) Axon degeneration: molecular mechanisms of a self-destruction pathway. J Cell Biol 196:7–18. doi:10.1083/jcb.201108111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Ginsberg MD (1997) The new language of cerebral ischemia. AJNR Am J Neuroradiol 18:1435–1445

    CAS  PubMed  Google Scholar 

  132. Teo L, Rosenfeld JV, Bourne JA (2012) Models of CNS injury in the nonhuman primate: a new era for treatment strategies. Transl Neurosci 3:181–195. doi:10.2478/s13380-012-0023-z

    Article  Google Scholar 

  133. Yiu G, He Z (2006) Glial inhibition of CNS axon regeneration. Nat Rev Neurosci 7:617–627

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Dickendesher TL, Baldwin KT, Mironova YA, Koriyama Y, Raiker SJ, Askew KL, Wood A, Geoffroy CG et al (2012) NgR1 and NgR3 are receptors for chondroitin sulfate proteoglycans. Nat Neurosci 15:703–712. doi:10.1038/nn.3070

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Marklund N, Fulp CT, Shimizu S, Puri R, McMillan A, Strittmatter SM, McIntosh TK (2006) Selective temporal and regional alterations of nogo-a and small proline-rich repeat protein 1A (SPRR1A) but not nogo-66 receptor (NgR) occur following traumatic brain injury in the rat. Exp Neurol 197:70–83. doi:10.1016/j.expneurol.2005.08.029

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Josephson A, Widenfalk J, Widmer HW, Olson L, Spenger C (2001) Nogo mRNA expression in adult and fetal human and rat nervous tissue and in weight drop injury. Exp Neurol 169:319–328

    Article  CAS  PubMed  Google Scholar 

  137. Guo Q, Li S, Su B (2007) Expression of oligodendrocyte myelin glycoprotein and its receptor NgR after the injury of rat central nervous system. Neurosci Lett 422:103–108

    Article  CAS  PubMed  Google Scholar 

  138. Zhou C, Li Y, Nanda A, Zhang JH (2003) HBO suppresses nogo-a, ng-R, or RhoA expression in the cerebral cortex after global ischemia. Biochem Biophys Res Commun 309:368–376

    Article  CAS  PubMed  Google Scholar 

  139. Cheatwood JL, Emerick AJ, Schwab ME, Kartje GL (2008) Nogo-a expression after focal ischemic stroke in the adult rat. Stroke 39:2091–2098

    Article  CAS  PubMed  Google Scholar 

  140. Eslamboli A, Grundy RI, Irving EA (2006) Time-dependent increase in nogo-a expression after focal cerebral ischemia in marmoset monkeys. Neurosci Lett 408:89–93

    Article  CAS  PubMed  Google Scholar 

  141. Gou X, Zhang Q, Xu N, Deng B, Wang H, Xu L, Wang Q (2013) Spatio-temporal expression of paired immunoglobulin-like receptor-B in the adult mouse brain after focal cerebral ischaemia. Brain Inj 27:1311–1315. doi:10.3109/02699052.2013.812241

    Article  PubMed  Google Scholar 

  142. Filbin MT (2008) PirB, a second receptor for the myelin inhibitors of axonal regeneration Nogo66, MAG, and OMgp: implications for regeneration in vivo. Neuron 60:740–742. doi:10.1016/j.neuron.2008.12.001

    Article  CAS  PubMed  Google Scholar 

  143. Irving EA, Vinson M, Rosin C, Roberts JC, Chapman DM, Facci L, Virley DJ, Skaper SD et al (2005) Identification of neuroprotective properties of anti-MAG antibody: a novel approach for the treatment of stroke? J Cereb Blood Flow Metab 25:98–107. doi:10.1038/sj.jcbfm.9600011

    Article  CAS  PubMed  Google Scholar 

  144. Markus TM, Tsai SY, Bollnow MR, Farrer RG, O'Brien TE, Kindler-Baumann DR, Rausch M, Rudin M et al (2005) Recovery and brain reorganization after stroke in adult and aged rats. Ann Neurol 58:950–953. doi:10.1002/ana.20676

    Article  PubMed  Google Scholar 

  145. Papadopoulos CM, Tsai SY, Alsbiei T, O'Brien TE, Schwab ME, Kartje GL (2002) Functional recovery and neuroanatomical plasticity following middle cerebral artery occlusion and IN-1 antibody treatment in the adult rat. Ann Neurol 51:433–441

    Article  PubMed  Google Scholar 

  146. Seymour AB, Andrews EM, Tsai SY, Markus TM, Bollnow MR, Brenneman MM, O'Brien TE, Castro AJ et al (2005) Delayed treatment with monoclonal antibody IN-1 1 week after stroke results in recovery of function and corticorubral plasticity in adult rats. J Cereb Blood Flow Metab 25:1366–1375. doi:10.1038/sj.jcbfm.9600134

    Article  CAS  PubMed  Google Scholar 

  147. Tsai S-Y, Papadopoulos CM, Schwab ME, Kartje GL (2011) Delayed anti-nogo-a therapy improves function after chronic stroke in adult rats. Stroke 42:186–190. doi:10.1161/strokeaha.110.590083

    Article  CAS  PubMed  Google Scholar 

  148. Tsai SY, Markus TM, Andrews EM, Cheatwood JL, Emerick AJ, Mir AK, Schwab ME, Kartje GL (2007) Intrathecal treatment with anti-nogo-a antibody improves functional recovery in adult rats after stroke. Exp Brain Res 182:261–266. doi:10.1007/s00221-007-1067-0

    Article  CAS  PubMed  Google Scholar 

  149. Wiessner C, Bareyre FM, Allegrini PR, Mir AK, Frentzel S, Zurini M, Schnell L, Oertle T et al (2003) Anti-nogo-a antibody infusion 24 hours after experimental stroke improved behavioral outcome and corticospinal plasticity in normotensive and spontaneously hypertensive rats. J Cereb Blood Flow Metab 23:154–165

    Article  CAS  PubMed  Google Scholar 

  150. Kilic E, Elali A, Kilic L, Guo Z, Ugur M, Uslu U, Bassetti CL, Schwab ME et al (2010) Role of nogo-a in neuronal survival in the reperfused ischemic brain. J Cereb Blood Flow Metab 30:969–984

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. Bourquin C, van der Haar ME, Anz D, Sandholzer N, Neumaier I, Endres S, Skerra A, Schwab ME et al (2008) DNA vaccination efficiently induces antibodies to nogo-a and does not exacerbate experimental autoimmune encephalomyelitis. Eur J Pharmacol 588:99–105. doi:10.1016/j.ejphar.2008.04.026

    Article  CAS  PubMed  Google Scholar 

  152. Lv J, Xu RX, Jiang XD, Lu X, Ke YQ, Cai YQ, Du MX, Hu C et al (2010) Passive immunization with LINGO-1 polyclonal antiserum afforded neuroprotection and promoted functional recovery in a rat model of spinal cord injury. Neuroimmunomodulation 17:270–278

    Article  CAS  PubMed  Google Scholar 

  153. Ji B, Li M, Wu WT, Yick LW, Lee X, Shao Z, Wang J, So KF et al (2006) LINGO-1 antagonist promotes functional recovery and axonal sprouting after spinal cord injury. Mol Cell Neurosci 33:311–320. doi:10.1016/j.mcn.2006.08.003

    Article  CAS  PubMed  Google Scholar 

  154. Lee JK, Kim JE, Sivula M, Strittmatter SM (2004) Nogo receptor antagonism promotes stroke recovery by enhancing axonal plasticity. J Neurosci 24:6209–6217. doi:10.1523/JNEUROSCI.1643-04.2004

    Article  CAS  PubMed  Google Scholar 

  155. Zhan H, Sun SJ, Cai J, Li YQ, Hu CL, Lee DH, So KF, Li X (2013) The effect of an NgR1 antagonist on the neuroprotection of cortical axons after cortical infarction in rats. Neurochem Res 38:1333–1340. doi:10.1007/s11064-013-1026-z

    Article  CAS  PubMed  Google Scholar 

  156. Cao Y, Shumsky JS, Sabol MA, Kushner RA, Strittmatter S, Hamers FP, Lee DH, Rabacchi SA et al (2008) Nogo-66 receptor antagonist peptide (NEP1-40) administration promotes functional recovery and axonal growth after lateral funiculus injury in the adult rat. Neurorehabil Neural Repair 22:262–278. doi:10.1177/1545968307308550

    Article  CAS  PubMed  Google Scholar 

  157. GrandPre T, Li S, Strittmatter SM (2002) Nogo-66 receptor antagonist peptide promotes axonal regeneration. Nature 417:547–551. doi:10.1038/417547a

    Article  CAS  PubMed  Google Scholar 

  158. Li S, Strittmatter SM (2003) Delayed systemic nogo-66 receptor antagonist promotes recovery from spinal cord injury. J Neurosci 23:4219–4227

    CAS  PubMed  Google Scholar 

  159. Zai L, Ferrari C, Dice C, Subbaiah S, Havton LA, Coppola G, Geschwind D, Irwin N et al (2011) Inosine augments the effects of a nogo receptor blocker and of environmental enrichment to restore skilled forelimb use after stroke. J Neurosci 31:5977–5988

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  160. Yang YS, Harel NY, Strittmatter SM (2009) Reticulon-4A (nogo-a) redistributes protein disulfide isomerase to protect mice from SOD1-dependent amyotrophic lateral sclerosis. J Neurosci 29:13850–13859. doi:10.1523/JNEUROSCI.2312-09.2009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  161. Pernet V, Joly S, Dalkara D, Schwarz O, Christ F, Schaffer D, Flannery JG, Schwab ME (2012) Neuronal nogo-a upregulation does not contribute to ER stress-associated apoptosis but participates in the regenerative response in the axotomized adult retina. Cell Death Differ 19:1096–1108

    Article  CAS  PubMed  Google Scholar 

  162. Omoto S, Ueno M, Mochio S, Takai T, Yamashita T (2010) Genetic deletion of paired immunoglobulin-like receptor B does not promote axonal plasticity or functional recovery after traumatic brain injury. J Neurosci 30:13045–13052. doi:10.1523/Jneurosci.3228-10.2010

    Article  CAS  PubMed  Google Scholar 

  163. Zheng BH, Atwal J, Ho C, Case L, He XL, Garcia KC, Steward O, Tessier-Lavigne M (2005) Genetic deletion of the nogo receptor does not reduce neurite inhibition in vitro or promote corticospinal tract regeneration in vivo. Proc Natl Acad Sci U S A 102:1205–1210. doi:10.1073/Pnas.0409026102

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  164. O'collins VE, Macleod MR, Donnan GA, Horky LL, van der Worp BH, Howells DW (2006) 1,026 experimental treatments in acute stroke. Ann Neurol 59:467–477. doi:10.1002/ana.20741

    Article  PubMed  CAS  Google Scholar 

  165. Bregman BS, Kunkelbagden E, Schnell L, Dai HN, Gao D, Schwab ME (1995) Recovery from spinal-cord injury mediated by antibodies to neurite growth-inhibitors. Nature 378:498–501. doi:10.1038/378498a0

    Article  CAS  PubMed  Google Scholar 

  166. Liebscher T, Schnell L, Schnell D, Scholl J, Schneider R, Gullo M, Fouad K, Mir A et al (2005) Nogo-a antibody improves regeneration and locomotion of spinal cord-injured rats. Ann Neurol 58:706–719. doi:10.1002/ana.20627

    Article  CAS  PubMed  Google Scholar 

  167. Merkler D, Metz GAS, Raineteau O, Dietz V, Schwab ME, Fouad K (2001) Locomotor recovery in spinal cord-injured rats treated with an antibody neutralizing the myelin-associated neurite growth inhibitor nogo-a. J Neurosci 21:3665–3673

    CAS  PubMed  Google Scholar 

  168. Schnell L, Schwab ME (1990) Axonal regeneration in the rat spinal cord produced by an antibody against myelin-associated neurite growth inhibitors. Nature 343:269–272. doi:10.1038/343269a0

    Article  CAS  PubMed  Google Scholar 

  169. Freund P, Schmidlin E, Wannier T, Bloch J, Mir A, Schwab ME, Rouiller EM (2009) Anti-nogo-a antibody treatment promotes recovery of manual dexterity after unilateral cervical lesion in adult primates—re-examination and extension of behavioral data. Eur J Neurosci 29:983–996

    Article  PubMed  PubMed Central  Google Scholar 

  170. Zörner B, Schwab ME (2010) Anti-nogo on the go: from animal models to a clinical trial. Ann N Y Acad Sci 1198:E22–E34

    Article  PubMed  Google Scholar 

  171. Hawryluk GWJ, Rowland J, Kwon BK, Fehlings MG (2008) Protection and repair of the injured spinal cord: a review of completed, ongoing, and planned clinical trials for acute spinal cord injury. Neurosurg Focus 25:E14. doi:10.3171/FOC.2008.25.11.E14

    Article  PubMed  Google Scholar 

  172. Fehlings MG, Theodore N, Harrop J, Maurais G, Kuntz C, Shaffrey CI, Kwon BK, Chapman J et al (2011) Phase I/IIa clinical trial of a recombinant rho protein antagonist in acute spinal cord injury. J Neurotrauma 28:787–796. doi:10.1089/neu.2011.1765

    Article  PubMed  Google Scholar 

  173. Cramer SC, Abila B, Scott NE, Simeoni M, Enney LA (2013) Safety, pharmacokinetics, and pharmacodynamics of escalating repeat doses of GSK249320 in patients with stroke. Stroke 44:1337–1342. doi:10.1161/STROKEAHA.111.674366

    Article  CAS  PubMed  Google Scholar 

  174. Fournier AE, Gould GC, Liu BP, Strittmatter SM (2002) Truncated soluble nogo receptor binds nogo-66 and blocks inhibition of axon growth by myelin. J Neurosci 22:8876–8883

    CAS  PubMed  Google Scholar 

  175. Li S, Liu BP, Budel S, Li M, Ji B, Walus L, Li W, Jirik A et al (2004) 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 24:10511–10520. doi:10.1523/JNEUROSCI.2828-04.2004

    Article  CAS  PubMed  Google Scholar 

  176. Wang XX, Baughman KW, Basso M, Strittmatter SM (2006) Delayed nogo receptor therapy improves recovery from spinal cord contusion. Ann Neurol 60:540–549. doi:10.1002/ana.20953

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  177. Wang X, Yigitkanli K, Kim CY, Sekine-Komo T, Wirak D, Frieden E, Bhargava A, Maynard G et al (2014) Human NgR-fc decoy protein via lumbar intrathecal bolus administration enhances recovery from rat spinal cord contusion. J Neurotrauma 31:1955–1966. doi:10.1089/neu.2014.3355

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The authors wish to acknowledge and thank C. Bernard for his useful comments on earlier versions of the article. A National Health and Medical Research Council (NHMRC) Senior Research Fellowship (APP1077677) supports JAB, and AGB is supported by an Australian Postgraduate Award (APA) Scholarship. An NHMRC Project Grant (APP108197) supported this work. The Australian Regenerative Medicine Institute is supported by grants from the State Government of Victoria and the Australian Government.

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    Anthony G. Boghdadi, Leon Teo & James A. Bourne

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Boghdadi, A.G., Teo, L. & Bourne, J.A. The Involvement of the Myelin-Associated Inhibitors and Their Receptors in CNS Plasticity and Injury. Mol Neurobiol 55, 1831–1846 (2018). https://doi.org/10.1007/s12035-017-0433-6

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