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Spinal Cord and Peripheral Nerve Regeneration Current Research and Future Possibilities

  • Wise YoungEmail author
  • Hilton M. Kaplan
Chapter

Abstract

Our nervous system is remarkably elegant but also exceedingly complex. These complexities create monumental hurdles to regeneration. The current state of the art in spinal cord and peripheral nerve regeneration are explored. Future possibilities are laid out – aiming ultimately not just to restore function but almost certainly to even enhance it.

Keywords

Spinal cord Peripheral nerve Nervous system Regeneration Future possibilities 

Abbreviations

Akt

Oncogene of transforming retrovirus AKT8 (also Akt1 and PKB)

ATF-2

Activating transcription factor 2

ATF-3

Activating transcription factor 3

BBI

Brain-to-brain interface

BDNF

Brain-derived neurotrophic factor

chABC

Chondroitinase ABC

cAMP

Cyclic adenosine monophosphate

Caspr

Contactin-associated protein

CE

Conformité Européenne

CNS

Central nervous system

CSPG

Chondroitin-6-sulfate proteoglycan

DREADDS

Designer Receptors Exclusively Activated by Designer Drugs

DRG

Dorsal root ganglia

EMG

Electromyography

FDA

Food and Drug Administration

FLAMES

Floating light-activated microelectrical stimulators

GFAP

Glial fibrillary acidic protein

GHBP

Glial hyaluronate-binding protein

HSPG

Heparin sulfate proteoglycan

IGF-1

Insulin-like growth factor-1

IL-1

Interleukin-1

IN-1

IgM antibody that inhibits axonal growth

KSPG

Keratin sulfate proteoglycan (KSPG)

MAG

Myelin-associated glycoprotein

mTOR

Mammalian target of rapamycin

NED

Neural Enhancement Divide

NEP1-40

Peptide 1–40 of Nogo that inhibits NgR

NG2

Neural/glial antigen 2 (includes CSPG4)

NGC

Nerve guidance conduit

NgR

Nogo receptor

NgR1

Nogo receptor 1

NgR3

Nogo receptor 3

NMES

Neuromuscular electrical stimulation

Nogo

Neuronal growth inhibitory molecule in myelin

Nogo-A

The A version of Nogo

Nogo-A/Nogo-B

Nogo-A and Nogo-B genes

NS2.0

Nervous System 2.0

NTR

Neurotrophin receptor (p75 receptor)

OmgP

Oligodendroglial myelin glycoprotein

p75

75 KD protein

PC12

Pheochromocytoma 12

PDGF

Platelet-derived growth factor

PDK1/2

Phosphoinositide-dependent protein kinase 1 and 2

PI3K

Phosphoinositol 3 kinase

PIP2

Phosphoinositol phosphate 2

PIP3

Phosphoinositol phosphate 3

PKA

Phosphokinase A

PKB

Phosphokinase B (also Akt) a serine/threonine protein kinase

PNS

Peripheral nervous system

PTEN

Phosphatase tensin homologue

Rheb1

Ras homologue enriched in brain 1

RhoA

Rho A

RhoK

Rho kinase

RPTPsigma

Receptor protein tyrosine phosphatase sigma

SCI

Spinal cord injury

STAT3

Signal transducer and activator of transcription 3

TSC1/2

Tuberous sclerosis 1 and 2

UCSD

University of California San Diego

References

  1. 1.
    Abdo A, Sahin M, Freedman DS, Cevik E, Spuhler PS, Unlu MS. Floating light-activated microelectrical stimulators tested in the rat spinal cord. J Neural Eng. 2015;8:056012.CrossRefGoogle Scholar
  2. 2.
    Abrous N, Guy J, Vigny A, Calas A, Le Moal M, Herman JP. Development of intracerebral dopaminergic grafts: a combined immunohistochemical and autoradiographic study of its time course and environmental influences. J Comp Neurol. 1988;273:26–41.PubMedCrossRefGoogle Scholar
  3. 3.
    AbudF EM, Ichiyama RM, Havton LA, Chang HH. Spinal stimulation of the upper lumbar spinal cord modulates urethral sphincter activity in rats after spinal cord injury. Am J Physiol Renal Physiol. 2015;308:F1032–40.CrossRefGoogle Scholar
  4. 4.
    Alam M, Garcia-Alias G, Shah PK, Gerasimenko Y, Zhong H, Roy RR, Edgerton VR. Evaluation of optimal electrode configurations for epidural spinal cord stimulation in cervical spinal cord injured rats. J Neurosci Methods. 2015;247:50–7.PubMedPubMedCentralCrossRefGoogle Scholar
  5. 5.
    Alluin O, Delivet-Mongrain H, Gauthier MK, Fehlings MG, Rossignol S, Karimi-Abdolrezaee S. Examination of the combined effects of chondroitinase ABC, growth factors and locomotor training following compressive spinal cord injury on neuroanatomical plasticity and kinematics. PLoS One. 2014;9:e111072.PubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    Angeli CA, Edgerton VR, Gerasimenko YP, Harkema SJ. Altering spinal cord excitability enables voluntary movements after chronic complete paralysis in humans. Brain. 2014;137:1394–409.PubMedPubMedCentralCrossRefGoogle Scholar
  7. 7.
    Anghelescu N, Petrescu A, Alexandrescu I. Therapy study on the experimental injury of spinal cord. IV. High doses of methyl-prednisolone. Rom J Neurol Psychiatry. 1995;33:241–9.PubMedGoogle Scholar
  8. 8.
    Angius D, Wang H, Spinner RJ, Gutierrez-Cotto Y, Yaszemski MJ, Windebank AJ. A systematic review of animal models used to study nerve regeneration in tissue-engineered scaffolds. Biomaterials. 2012;33:8034–9.PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Azmitia EC, Whitaker PM. Formation of a glial scar following microinjection of fetal neurons into the hippocampus or midbrain of the adult rat: an immunocytochemical study. Neurosci Lett. 1983;38:145–50.PubMedCrossRefGoogle Scholar
  10. 10.
    Bajrovic F, Remskar M, Sketelj J. Prior collateral sprouting enhances elongation rate of sensory axons regenerating through acellular distal segment of a crushed peripheral nerve. J Peripher Nerv Syst. 1999;4:5–12.PubMedGoogle Scholar
  11. 11.
    Bandtlow C, Schiweck W, Tai HH, Schwab ME, Skerra A. The Escherichia coli-derived Fab fragment of the IgM/kappa antibody IN-1 recognizes and neutralizes myelin-associated inhibitors of neurite growth. Eur J Biochem. 1996;241:468–75.PubMedCrossRefGoogle Scholar
  12. 12.
    Bandtlow CE, Schwab ME. NI-35/250/nogo-a: a neurite growth inhibitor restricting structural plasticity and regeneration of nerve fibers in the adult vertebrate CNS. Glia. 2000;29:175–81.PubMedCrossRefGoogle Scholar
  13. 13.
    Bandtlow CE. Regeneration in the central nervous system. Exp Gerontol. 2003;38:79–86.PubMedCrossRefGoogle Scholar
  14. 14.
    Bar-Cohen Y, Loeb GE, Pruetz JD, Silka MJ, Guerra C, Vest AN, Zhou L, Chmait RH. Preclinical testing and optimization of a novel fetal micropacemaker. Heart Rhythm. 2015;12:1683–90.PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Baranowski AP, Priestley JV, McMahon SB. The consequence of delayed versus immediate nerve repair on the properties of regenerating sensory nerve fibers in the adult rat. Neurosci Lett. 1994;168:197–200.PubMedCrossRefGoogle Scholar
  16. 16.
    Barritt AW, Davies M, Marchand F, Hartley R, Grist J, Yip P, McMahon SB, Bradbury EJ. Chondroitinase ABC promotes sprouting of intact and injured spinal systems after spinal cord injury. J Neurosci. 2006;26:10856–67.PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    Barton WA, Liu BP, Tzvetkova D, Jeffrey PD, Fournier AE, Sah D, Cate R, Strittmatter SM, Nikolov DB. Structure and axon outgrowth inhibitor binding of the Nogo-66 receptor and related proteins. EMBO J. 2003;22:3291–302.PubMedPubMedCentralCrossRefGoogle Scholar
  18. 18.
    Bartsch U, Bandtlow CE, Schnell L, Bartsch S, Spillmann AA, Rubin BP, Hillenbrand R, Montag D, Schwab ME, Schachner M. Lack of evidence that myelin-associated glycoprotein is a major inhibitor of axonal regeneration in the CNS. Neuron. 1995;15:1375–81.PubMedCrossRefGoogle Scholar
  19. 19.
    Beattie MS, Bresnahan JC, Komon J, Tovar CA, Van Meter M, Anderson DK, Faden AI, Hsu CY, Noble LJ, Salzman S, Young W. Endogenous repair after spinal cord contusion injuries in the rat. Exp Neurol. 1997;148:453–63.PubMedCrossRefGoogle Scholar
  20. 20.
    Behrman AL, Harkema SJ. Physical rehabilitation as an agent for recovery after spinal cord injury. Phys Med Rehabil Clin N Am. 2007;18:183–202.PubMedCrossRefGoogle Scholar
  21. 21.
    Belkas SJ, Shoichet SM, Midha R. Peripheral nerve regeneration through guidance tubes. Neurol Res. 2004;26:151–60.PubMedCrossRefGoogle Scholar
  22. 22.
    Berger TW, Glanzman DL. Toward replacement parts for the brain: implantable biomimetic electronics as neural prostheses. Cambridge: MIT Press; 2005.Google Scholar
  23. 23.
    Bernstein JJ, Bernstein ME. Effect of glial-ependymal scar and teflon arrest on the regenerative capacity of goldfish spinal cord. Exp Neurol. 1967;19:25–32.PubMedCrossRefGoogle Scholar
  24. 24.
    Bignami A. The role of astrocytes in CNS regeneration. J Neurosurg Sci. 1984;28:127–32.PubMedGoogle Scholar
  25. 25.
    Birch R, Dunkerton M, Bonney G, Jamieson AM. Experience with the free vascularized ulnar nerve graft in repair of supraclavicular lesions of the brachial plexus. Clin Orthop Relat Res. 1988;237:96–104.Google Scholar
  26. 26.
    Bisby MA, Pollock B. Increased regeneration rate in peripheral nerve axons following double lesions: enhancement of the conditioning lesion phenomenon. J Neurobiol. 1983;14:467–72.PubMedCrossRefGoogle Scholar
  27. 27.
    Bisby MA, Keen P. The effect of a conditioning lesion on the regeneration rate of peripheral nerve axons containing substance P. Brain Res. 1985;336:201–6.PubMedCrossRefGoogle Scholar
  28. 28.
    Bisby MA, Keen P. Regeneration of primary afferent neurons containing substance P-like immunoreactivity. Brain Res. 1986;365:85–95.PubMedCrossRefGoogle Scholar
  29. 29.
    Bolesta MJ, Garrett Jr WE, Ribbeck BM, Glisson RR, Seaber AV, Goldner JL. Immediate and delayed neurorrhaphy in a rabbit model: a functional, histologic, and biochemical comparison. J Hand Surg Am. 1988;13:352–7.PubMedCrossRefGoogle Scholar
  30. 30.
    Borgens RB, Roederer E, Cohen MJ. Enhanced spinal cord regeneration in lamprey by applied electric fields. Science. 1981;213:611–7.PubMedCrossRefGoogle Scholar
  31. 31.
    Borgens RB, Blight AR, Murphy DJ, Stewart L. Transected dorsal column axons within the guinea pig spinal cord regenerate in the presence of an applied electric field. J Comp Neurol. 1986;250:168–80.PubMedCrossRefGoogle Scholar
  32. 32.
    Bottai D, Scesa G, Cigognini D, Adami R, Nicora E, Abrignani S, Di Giulio AM, Gorio A. Third trimester NG2-positive amniotic fluid cells are effective in improving repair in spinal cord injury. Exp Neurol. 2014;254C:121–33.CrossRefGoogle Scholar
  33. 33.
    Bovolenta P, Wandosell F, Nieto-Sampedro M. Neurite outgrowth over resting and reactive astrocytes. Restor Neurol Neurosci. 1991;2:221–8.PubMedGoogle Scholar
  34. 34.
    Bovolenta P, Wandosell F, Nieto-Sampedro M. CNS glial scar tissue: a source of molecules which inhibit central neurite outgrowth. Prog Brain Res. 1992;94:367–79.PubMedCrossRefGoogle Scholar
  35. 35.
    Bradbury EJ, Moon LD, Popat RJ, King VR, Bennett GS, Patel PN, Fawcett JW, McMahon SB. Chondroitinase ABC promotes functional recovery after spinal cord injury. Nature. 2002;416:636–40.PubMedCrossRefGoogle Scholar
  36. 36.
    Bregman BS, Kunkel-Bagden E, Schnell L, Dai HN, Gao D, Schwab ME. Recovery from spinal cord injury mediated by antibodies to neurite growth inhibitors. Nature. 1995;378:498–501.PubMedCrossRefGoogle Scholar
  37. 37.
    Brittis PA, Flanagan JG. Nogo domains and a Nogo receptor: implications for axon regeneration. Neuron. 2001;30:11–4.PubMedCrossRefGoogle Scholar
  38. 38.
    Broggini T, Nitsch R, Savaskan NE. Plasticity-related gene 5 (PRG5) induces filopodia and neurite growth and impedes lysophosphatidic acid- and nogo-A-mediated axonal retraction. Mol Biol Cell. 2010;21:521–37.PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Brosamle C, Huber AB, Fiedler M, Skerra A, Schwab ME. Regeneration of lesioned corticospinal tract fibers in the adult rat induced by a recombinant, humanized IN-1 antibody fragment. J Neurosci. 2000;20:8061–8.PubMedGoogle Scholar
  40. 40.
    Brus-Ramer M, Carmel JB, Chakrabarty S, Martin JH. Electrical stimulation of spared corticospinal axons augments connections with ipsilateral spinal motor circuits after injury. J Neurosci. 2007;27:13793–801.PubMedCrossRefGoogle Scholar
  41. 41.
    Brus-Ramer M, Carmel JB, Martin JH. Motor cortex bilateral motor representation depends on subcortical and interhemispheric interactions. J Neurosci. 2009;29:6196–206.PubMedPubMedCentralCrossRefGoogle Scholar
  42. 42.
    Buffo A, Zagrebelsky M, Huber AB, Skerra A, Schwab ME, Strata P, Rossi F. Application of neutralizing antibodies against NI-35/250 myelin-associated neurite growth inhibitory proteins to the adult rat cerebellum induces sprouting of uninjured purkinje cell axons. J Neurosci. 2000;20:2275–86.PubMedGoogle Scholar
  43. 43.
    Bunge MB. Novel combination strategies to repair the injured mammalian spinal cord. J Spinal Cord Med. 2008;31:262–9.PubMedPubMedCentralCrossRefGoogle Scholar
  44. 44.
    Cafferty WB, Yang SH, Duffy PJ, Li S, Strittmatter SM. Functional axonal regeneration through astrocytic scar genetically modified to digest chondroitin sulfate proteoglycans. J Neurosci. 2007;27:2176–85.PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Cafferty WB, Duffy P, Huebner E, Strittmatter SM. MAG and OMgp synergize with Nogo-A to restrict axonal growth and neurological recovery after spinal cord trauma. J Neurosci. 2010;30:6825–37.PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Cai D, Shen Y, De Bellard M, Tang S, Filbin MT. Prior exposure to neurotrophins blocks inhibition of axonal regeneration by MAG and myelin via a cAMP-dependent mechanism. Neuron. 1999;22:89–101.PubMedCrossRefGoogle Scholar
  47. 47.
    Cai D, Qiu J, Cao Z, McAtee M, Bregman BS, Filbin MT. Neuronal cyclic AMP controls the developmental loss in ability of axons to regenerate. J Neurosci. 2001;21:4731–9.PubMedGoogle Scholar
  48. 48.
    Canavero S. HEAVEN: The head anastomosis venture Project outline for the first human head transplantation with spinal linkage (GEMINI). Surg Neurol Int. 2013;4 Suppl 1:S335–42.PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Carlstedt T, Cullheim S, Risling M, Ulfhake B. Mammalian root-spinal cord regeneration. Prog Brain Res. 1988;8:225–9.CrossRefGoogle Scholar
  50. 50.
    Carlstedt T. Reinnervation of the mammalian spinal cord after neonatal dorsal root crush. J Neurocytol. 1988;17:335–50.PubMedCrossRefGoogle Scholar
  51. 51.
    Carmel JB, Berrol LJ, Brus-Ramer M, Martin JH. Chronic electrical stimulation of the intact corticospinal system after unilateral injury restores skilled locomotor control and promotes spinal axon outgrowth. J Neurosci. 2010;30:10918–26.PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Carmel JB, Kimura H, Berrol LJ, Martin JH. Motor cortex electrical stimulation promotes axon outgrowth to brain stem and spinal targets that control the forelimb impaired by unilateral corticospinal injury. Eur J Neurosci. 2013;37:1090–102.PubMedPubMedCentralCrossRefGoogle Scholar
  53. 53.
    Carmel JB, Kimura H, Martin JH. Electrical stimulation of motor cortex in the uninjured hemisphere after chronic unilateral injury promotes recovery of skilled locomotion through ipsilateral control. J Neurosci. 2014;34:462–6.PubMedPubMedCentralCrossRefGoogle Scholar
  54. 54.
    Carmel JB, Martin JH. Motor cortex electrical stimulation augments sprouting of the corticospinal tract and promotes recovery of motor function. Front Integr Neurosci. 2014;8:51.PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Carter LM, McMahon SB, Bradbury EJ. Delayed treatment with chondroitinase ABC reverses chronic atrophy of rubrospinal neurons following spinal cord injury. Exp Neurol. 2011;228:149–56.PubMedCrossRefGoogle Scholar
  56. 56.
    Chalecka-Franaszek E, Chuang DM. Lithium activates the serine/threonine kinase Akt-1 and suppresses glutamate-induced inhibition of Akt-1 activity in neurons. Proc Natl Acad Sci U S A. 1999;96:8745–50.PubMedPubMedCentralCrossRefGoogle Scholar
  57. 57.
    Chen MS, Huber AB, van der Haar ME, Frank M, Schnell L, Spillmann AA, Christ F, Schwab ME. Nogo-A is a myelin-associated neurite outgrowth inhibitor and an antigen for monoclonal antibody IN-1. Nature. 2000;403:434–9.PubMedCrossRefGoogle Scholar
  58. 58.
    Chen X, Choo H, Huang XP, Yang X, Stone O, Roth BL, Jin J. The first structure-activity relationship studies for designer receptors exclusively activated by designer drugs. ACS Chem Neurosci. 2015;6:476–84.PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Chong MS, Woolf CJ, Haque NS, Anderson PN. Axonal regeneration from injured dorsal roots into the spinal cord of adult rats. J Comp Neurol. 1999;410:42–54.PubMedCrossRefGoogle Scholar
  60. 60.
    Chuang DC, Chen KT. The possibility and potential feasibility of putting an extra functioning free muscle transplant onto a normal limb: experimental rat study. Plast Reconstr Surg. 2011;128:853–9.PubMedCrossRefGoogle Scholar
  61. 61.
    Clemente CD. Regeneration in the vertebrate central nervous system. Int Rev Neurobiol. 1964;6:257–301.PubMedCrossRefGoogle Scholar
  62. 62.
    Colen KL, Choi M, Chiu DT. Nerve grafts and conduits. Plast Reconstr Surg. 2009;124(6 Suppl):e386–94.PubMedCrossRefGoogle Scholar
  63. 63.
    Coles CH, Shen Y, Tenney AP, Siebold C, Sutton GC, Lu W, Gallagher JT, Jones EY, Flanagan JG, Aricescu AR. Proteoglycan-specific molecular switch for RPTPsigma clustering and neuronal extension. Science. 2011;332:484–8.PubMedPubMedCentralCrossRefGoogle Scholar
  64. 64.
    Connor JR, Bernstein JJ. Astrocytes in rat fetal cerebral cortical homografts following implantation into adult rat spinal cord. Brain Res. 1987;409:62–70.PubMedCrossRefGoogle Scholar
  65. 65.
    Courtine G, Harkema SJ, Dy CJ, Gerasimenko YP, Dyhre-Poulsen P. Modulation of multisegmental monosynaptic responses in a variety of leg muscles during walking and running in humans. J Physiol. 2007;582:1125–39.PubMedPubMedCentralCrossRefGoogle Scholar
  66. 66.
    Dagnelie G. Retinal implants: emergence of a multidisciplinary field. Curr Opin Neurol. 2012;25:67–75.PubMedCrossRefGoogle Scholar
  67. 67.
    Dahl D, Perides G, Bignami A. Axonal regeneration in old multiple sclerosis plaques. Immunohistochemical study with monoclonal antibodies to phosphorylated and non-phosphorylated neurofilament proteins. Acta Neuropathol. 1989;79:154–9.PubMedCrossRefGoogle Scholar
  68. 68.
    Dahlin LB. Stimulation of regeneration of the sciatic nerve by experimentally induced inflammation in rats. Scand J Plast Reconstr Surg Hand Surg. 1992;26:121–5.PubMedCrossRefGoogle Scholar
  69. 69.
    Dahlin LB, Kanje M. Conditioning effect induced by chronic nerve compression. An experimental study of the sciatic and tibial nerves of rats. Scand J Plast Reconstr Surg Hand Surg. 1992;26:37–41.PubMedCrossRefGoogle Scholar
  70. 70.
    Dahlin LB, Thambert C. Acute nerve compression at low pressures has a conditioning lesion effect on rat sciatic nerves. Acta Orthop Scand. 1993;64:479–81.PubMedCrossRefGoogle Scholar
  71. 71.
    Daly W, Yao L, Zeugolis D, Windebank A, Pandit A. A biomaterials approach to peripheral nerve regeneration: bridging the peripheral nerve gap and enhancing functional recovery. J R Soc Interface. 2012;9:202–21.PubMedCrossRefGoogle Scholar
  72. 72.
    Danilov CA, Steward O. Conditional genetic deletion of PTEN after a spinal cord injury enhances regenerative growth of CST axons and motor function recovery in mice. Exp Neurol. 2015;266:147–60.PubMedPubMedCentralCrossRefGoogle Scholar
  73. 73.
    Das GD, Ross DT. Neural transplantation: autoradiographic analysis of histogenesis in neocortical transplants. Int J Dev Neurosci. 1986;4:69–79.PubMedCrossRefGoogle Scholar
  74. 74.
    David S, Aguayo AJ. Axonal elongation into peripheral nervous system “bridges” after central nervous system injury in adult rats. Science. 1981;214:931–3.PubMedCrossRefGoogle Scholar
  75. 75.
    Davies SJ, Fitch MT, Memberg SP, Hall AK, Raisman G, Silver J. Regeneration of adult axons in white matter tracts of the central nervous system. Nature. 1997;390:680–3.PubMedGoogle Scholar
  76. 76.
    de la Torre JC, Hill PK, Gonzalez-Carvajal M, Parker Jr JC. Evaluation of transected spinal cord regeneration in the rat. Exp Neurol. 1984;84:188–206.PubMedCrossRefGoogle Scholar
  77. 77.
    Dechant G, Barde YA. The neurotrophin receptor p75(NTR): novel functions and implications for diseases of the nervous system. Nat Neurosci. 2002;5:1131–6.PubMedCrossRefGoogle Scholar
  78. 78.
    Delcroix JD, Averill S, Fernandes K, Tomlinson DR, Priestley JV, Fernyhough P. Axonal transport of activating transcription factor-2 is modulated by nerve growth factor in nociceptive neurons. J Neurosci. 1999;19:RC24.PubMedGoogle Scholar
  79. 79.
    Deng WP, Yang CC, Yang LY, Chen CW, Chen WH, Yang CB, Chen YH, Lai WF, Renshaw PF. Extracellular matrix-regulated neural differentiation of human multipotent marrow progenitor cells enhances functional recovery after spinal cord injury. Spine J. 2014;14:2488–99.PubMedPubMedCentralCrossRefGoogle Scholar
  80. 80.
    Dickendesher TL, Baldwin KT, Mironova YA, Koriyama Y, Raiker SJ, Askew KL, Wood A, Geoffroy CG, Zheng B, Liepmann CD, Katagiri Y, Benowitz LI, Geller HM, Giger RJ. NgR1 and NgR3 are receptors for chondroitin sulfate proteoglycans. Nat Neurosci. 2012;15:703–12.PubMedPubMedCentralCrossRefGoogle Scholar
  81. 81.
    Dill J, Wang H, Zhou F, Li S. Inactivation of glycogen synthase kinase 3 promotes axonal growth and recovery in the CNS. J Neurosci. 2008;28:8914–28.PubMedCrossRefGoogle Scholar
  82. 82.
    Dimou L, Schnell L, Montani L, Duncan C, Simonen M, Schneider R, Liebscher T, Gullo M, Schwab ME. Nogo-A-deficient mice reveal strain-dependent differences in axonal regeneration. J Neurosci. 2006;26:5591–603.PubMedCrossRefGoogle Scholar
  83. 83.
    Dobkin B, Apple D, Barbeau H, Basso M, Behrman A, Deforge D, Ditunno J, Dudley G, Elashoff R, Fugate L, Harkema S, Saulino M, Scott M. Spinal cord injury locomotor trial, g. weight-supported treadmill vs over-ground training for walking after acute incomplete SCI. Neurology. 2006;66:484–93.PubMedPubMedCentralCrossRefGoogle Scholar
  84. 84.
    Dodd DA, Niederoest B, Bloechlinger S, Dupuis L, Loeffler JP, Schwab ME. Nogo-A, −B, and -C are found on the cell surface and interact together in many different cell types. J Biol Chem. 2005;280:12494–502.PubMedCrossRefGoogle Scholar
  85. 85.
    Du K, Zheng S, Zhang Q, Li S, Gao X, Wang J, Jiang L, Liu K. Pten deletion promotes regrowth of corticospinal tract axons 1 year after spinal cord injury. J Neurosci. 2015;35:9754–63.PubMedCrossRefGoogle Scholar
  86. 86.
    Duan Y, Giger RJ. A new role for RPTPsigma in spinal cord injury: signaling chondroitin sulfate proteoglycan inhibition. Sci Signal. 2010;3:pe6.PubMedCrossRefGoogle Scholar
  87. 87.
    Dy CJ, Gerasimenko YP, Edgerton VR, Dyhre-Poulsen P, Courtine G, Harkema SJ. Phase-dependent modulation of percutaneously elicited multisegmental muscle responses after spinal cord injury. J Neurophysiol. 2010;103:2808–20.PubMedPubMedCentralCrossRefGoogle Scholar
  88. 88.
    Dyck SM, Alizadeh A, Santhosh KT, Proulx EH, Wu CL, Karimi-Abdolrezaee S. Chondroitin sulfate proteoglycans negatively modulate spinal cord neural precursor cells by signaling through LAR and RPTPsigma and modulation of the Rho/ROCK pathway. Stem Cells. 2015;33:2550–63.PubMedCrossRefGoogle Scholar
  89. 89.
    Ebner FF, Erzurumlu RS, Lee SM. Peripheral nerve damage facilitates functional innervation of brain grafts in adult sensory cortex. Proc Natl Acad Sci U S A. 1989;86:730–4.PubMedPubMedCentralCrossRefGoogle Scholar
  90. 90.
    Edgerton VR, Harkema S. Epidural stimulation of the spinal cord in spinal cord injury: current status and future challenges. Expert Rev Neurother. 2011;11:1351–3.PubMedPubMedCentralCrossRefGoogle Scholar
  91. 91.
    Eichhorst H, Naunyn B. Ueber die Regeneration und Veränderungen im Rückenmarke nach streckenweiser totaler Zerstörung desslben. Naunyn Schmiedebergs Arch Exp Pathol Pharmakol. 1874;2:225–53.CrossRefGoogle Scholar
  92. 92.
    Elzinga K, Tyreman N, Ladak A, Savaryn B, Olson J, Gordon T. Brief electrical stimulation improves nerve regeneration after delayed repair in Sprague Dawley rats. Exp Neurol. 2015;269:142–53.PubMedCrossRefGoogle Scholar
  93. 93.
    Esmaeili M, Berry M, Logan A, Ahmed Z. Decorin treatment of spinal cord injury. Neural Regen Res. 2014;9:1653–6.PubMedPubMedCentralCrossRefGoogle Scholar
  94. 94.
    Fakhoury M. Spinal cord injury: overview of experimental approaches used to restore locomotor activity. Rev Neurosci. 2015;26:397–405.PubMedCrossRefGoogle Scholar
  95. 95.
    Fallon JR. Neurite guidance by non-neuronal cells in culture: preferential outgrowth of peripheral neurites on glial as compared to nonglial cell surfaces. J Neurosci. 1985;5:3169–77.PubMedGoogle Scholar
  96. 96.
    Fawcett JW. The extracellular matrix in plasticity and regeneration after CNS injury and neurodegenerative disease. Prog Brain Res. 2015;218:213–26.PubMedCrossRefGoogle Scholar
  97. 97.
    Filous AR, Miller JH, Coulson-Thomas YM, Horn KP, Alilain WJ, Silver J. Immature astrocytes promote CNS axonal regeneration when combined with chondroitinase ABC. Dev Neurobiol. 2010;70:826–41.PubMedPubMedCentralCrossRefGoogle Scholar
  98. 98.
    Fontoura P, Ho PP, DeVoss J, Zheng B, Lee BJ, Kidd BA, Garren H, Sobel RA, Robinson WH, Tessier-Lavigne M, Steinman L. Immunity to the extracellular domain of Nogo-A modulates experimental autoimmune encephalomyelitis. J Immunol. 2004;173:6981–92.PubMedCrossRefGoogle Scholar
  99. 99.
    Fouad K, Schnell L, Bunge MB, Schwab ME, Liebscher T, Pearse DD. Combining Schwann cell bridges and olfactory-ensheathing glia grafts with chondroitinase promotes locomotor recovery after complete transection of the spinal cord. J Neurosci. 2005;25:1169–78.PubMedCrossRefGoogle Scholar
  100. 100.
    Fournier AE, Gould GC, Liu BP, Strittmatter SM. Truncated soluble Nogo receptor binds Nogo-66 and blocks inhibition of axon growth by myelin. J Neurosci. 2002;22:8876–83.PubMedGoogle Scholar
  101. 101.
    Fournier AE, Takizawa BT, Strittmatter SM. Rho kinase inhibition enhances axonal regeneration in the injured CNS. J Neurosci. 2003;23:1416–23.PubMedGoogle Scholar
  102. 102.
    Frank M, Schaeren-Wiemers N, Schneider R, Schwab ME. Developmental expression pattern of the myelin proteolipid MAL indicates different functions of MAL for immature Schwann cells and in a late step of CNS myelinogenesis. J Neurochem. 1999;73:587–97.PubMedCrossRefGoogle Scholar
  103. 103.
    Frisen J, Haegerstrand A, Fried K, Piehl F, Cullheim S, Risling M. Adhesive/repulsive properties in the injured spinal cord: relation to myelin phagocytosis by invading macrophages. Exp Neurol. 1994;129:183–93.PubMedCrossRefGoogle Scholar
  104. 104.
    Fry EJ, Chagnon MJ, Lopez-Vales R, Tremblay ML, David S. Corticospinal tract regeneration after spinal cord injury in receptor protein tyrosine phosphatase sigma deficient mice. Glia. 2010;58:423–33.PubMedGoogle Scholar
  105. 105.
    Fu R, Tang Y, Ling ZM, Li YQ, Cheng X, Song FH, Zhou LH, Wu W. Lithium enhances survival and regrowth of spinal motoneurons after ventral root avulsion. BMC Neurosci. 2014;15:84.PubMedPubMedCentralCrossRefGoogle Scholar
  106. 106.
    Fuss B, Pott U, Fischer P, Schwab ME, Schachner M. Identification of a cDNA clone specific for the oligodendrocyte-derived repulsive extracellular matrix molecule J1-160/180. J Neurosci Res. 1991;29:299–307.PubMedCrossRefGoogle Scholar
  107. 107.
    Garcia-Alias G, Barkhuysen S, Buckle M, Fawcett JW. Chondroitinase ABC treatment opens a window of opportunity for task-specific rehabilitation. Nat Neurosci. 2009;12:1145–51.PubMedCrossRefGoogle Scholar
  108. 108.
    Garcia-Alias G, Truong K, Shah PK, Roy RR, Edgerton VR. Plasticity of subcortical pathways promote recovery of skilled hand function in rats after corticospinal and rubrospinal tract injuries. Exp Neurol. 2015;266:112–9.PubMedCrossRefGoogle Scholar
  109. 109.
    Gates MA, Fillmore H, Steindler DA. Chondroitin sulfate proteoglycan and tenascin in the wounded adult mouse neostriatum in vitro: dopamine neuron attachment and process outgrowth. J Neurosci. 1996;16:8005–18.PubMedGoogle Scholar
  110. 110.
    Gattuso JM, Glasby MA, Gschmeissner SE, Norris RW. A comparison of immediate and delayed repair of peripheral nerves using freeze-thawed autologous skeletal muscle grafts – in the rat. Br J Plast Surg. 1989;42:306–13.PubMedCrossRefGoogle Scholar
  111. 111.
    George SC, Boyce DE. An evidence-based structured review to assess the results of common peroneal nerve repair. Plast Reconstr Surg. 2014;134:302e–11.PubMedCrossRefGoogle Scholar
  112. 112.
    Giulian D, Li J, Li X, George J, Rutecki PA. The impact of microglia-derived cytokines upon gliosis in the CNS. Dev Neurosci. 1994;16:128–36.PubMedCrossRefGoogle Scholar
  113. 113.
    Goldshmit Y, Frisca F, Pinto AR, Pebay A, Tang JK, Siegel AL, Kaslin J, Currie PD. Fgf2 improves functional recovery-decreasing gliosis and increasing radial glia and neural progenitor cells after spinal cord injury. Brain Behav. 2014;4:187–200.PubMedPubMedCentralCrossRefGoogle Scholar
  114. 114.
    Gonzenbach RR, Zoerner B, Schnell L, Weinmann O, Mir AK, Schwab ME. Delayed anti-nogo-a antibody application after spinal cord injury shows progressive loss of responsiveness. J Neurotrauma. 2012;29:567–78.PubMedCrossRefGoogle Scholar
  115. 115.
    GrandPre T, Nakamura F, Vartanian T, Strittmatter SM. Identification of the Nogo inhibitor of axon regeneration as a Reticulon protein. Nature. 2000;403:439–44.PubMedCrossRefGoogle Scholar
  116. 116.
    Grimpe B, Silver J. A novel DNA enzyme reduces glycosaminoglycan chains in the glial scar and allows microtransplanted dorsal root ganglia axons to regenerate beyond lesions in the spinal cord. J Neurosci. 2004;24:1393–7.PubMedCrossRefGoogle Scholar
  117. 117.
    Guest JD, Hesse D, Schnell L, Schwab ME, Bunge MB, Bunge RP. Influence of IN-1 antibody and acidic FGF-fibrin glue on the response of injured corticospinal tract axons to human Schwann cell grafts. J Neurosci Res. 1997;50:888–905.PubMedCrossRefGoogle Scholar
  118. 118.
    Guest JD, Rao A, Olson L, Bunge MB, Bunge RP. The ability of human Schwann cell grafts to promote regeneration in the transected nude rat spinal cord. Exp Neurol. 1997;148:502–22.PubMedCrossRefGoogle Scholar
  119. 119.
    Guth L, Albuquerque EX, Deshpande SS, Barrett CP, Donati EJ, Warnick JE. Ineffectiveness of enzyme therapy on regeneration in the transected spinal cord of the rat. J Neurosurg. 1980;52:73–86.PubMedCrossRefGoogle Scholar
  120. 120.
    Guth L, Barrett CP, Donati EJ, Deshpande SS, Albuquerque EX. Histopathological reactions and axonal regeneration in the transected spinal cord of Hibernating squirrels. J Comp Neurol. 1981;203:297–308.PubMedCrossRefGoogle Scholar
  121. 121.
    Guth L, Barrett CP, Donati EJ, Anderson FD, Smith MV, Lifson M. Essentiality of a specific cellular terrain for growth of axons into a spinal cord lesion. Exp Neurol. 1985;88:1–12.PubMedCrossRefGoogle Scholar
  122. 122.
    Gutmann E, Guttmann L, Medawar PB, Young JZ. The rate of regeneration of nerve. J Exp Biol. 1942;19:14–44.Google Scholar
  123. 123.
    Hall S, Berry M. Electron microscopic study of the interaction of axons and glia at the site of anastomosis between the optic nerve and cellular or acellular sciatic nerve grafts. J Neurocytol. 1989;18:171–84.PubMedCrossRefGoogle Scholar
  124. 124.
    Han N, Xu CG, Wang TB, Kou YH, Yin XF, Zhang PX, Xue F. Electrical stimulation does not enhance nerve regeneration if delayed after sciatic nerve injury: the role of fibrosis. Neural Regen Res. 2015;10:90–4.PubMedPubMedCentralCrossRefGoogle Scholar
  125. 125.
    Hanada M, Tsutsumi K, Arima H, Shinjo R, Sugiura Y, Imagama S, Ishiguro N, Matsuyama Y. Evaluation of the effect of tranilast on rats with spinal cord injury. J Neurol Sci. 2014;346:209–15.PubMedCrossRefGoogle Scholar
  126. 126.
    Hanell A, Clausen F, Bjork M, Jansson K, Philipson O, Nilsson LN, Hillered L, Weinreb PH, Lee D, McIntosh TK, Gimbel DA, Strittmatter SM, Marklund N. Genetic deletion and pharmacological inhibition of Nogo-66 receptor impairs cognitive outcome after traumatic brain injury in mice. J Neurotrauma. 2010;27:1297–309.PubMedPubMedCentralCrossRefGoogle Scholar
  127. 127.
    Harkema SJ. Plasticity of interneuronal networks of the functionally isolated human spinal cord. Brain Res Rev. 2008;57:255–64.PubMedCrossRefGoogle Scholar
  128. 128.
    Harkema S, Gerasimenko Y, Hodes J, Burdick J, Angeli C, Chen Y, Ferreira C, Willhite A, Rejc E, Grossman RG, Edgerton VR. Effect of epidural stimulation of the lumbosacral spinal cord on voluntary movement, standing, and assisted stepping after motor complete paraplegia: a case study. Lancet. 2011;377:1938–47.PubMedPubMedCentralCrossRefGoogle Scholar
  129. 129.
    Harkema S, Behrman A, Barbeau H. Evidence-based therapy for recovery of function after spinal cord injury. Handb Clin Neurol. 2012;109:259–74.PubMedCrossRefGoogle Scholar
  130. 130.
    Hendel A, Bak RO, Clark JT, Kennedy AB, Ryan DE, Roy S, Steinfeld I, Lunstad BD, Kaiser RJ, Wilkens AB, Bacchetta R, Tsalenko A, Dellinger D, Bruhn L, Porteus MH. Chemically modified guide RNAs enhance CRISPR-Cas genome editing in human primary cells. Nat Biotechnol. 2015;33(9):985–9.PubMedPubMedCentralCrossRefGoogle Scholar
  131. 131.
    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.PubMedCrossRefGoogle Scholar
  132. 132.
    Hill CE, Beattie MS, Bresnahan JC. Degeneration and sprouting of identified descending supraspinal axons after contusive spinal cord injury in the rat. Exp Neurol. 2001;171:153–69.PubMedCrossRefGoogle Scholar
  133. 133.
    Hinckley CA, Alaynick WA, Gallarda BW, Hayashi M, Hilde KL, Driscoll SP, Dekker JD, Tucker HO, Sharpee TO, Pfaff SL. Spinal locomotor circuits develop using hierarchical rules based on motorneuron position and identity. Neuron. 2015;87:1008–21.PubMedPubMedCentralCrossRefGoogle Scholar
  134. 134.
    Hoffman-Kim D, Mitchel JA, Bellamkonda RV. Topography, cell response, and nerve regeneration. Annu Rev Biomed Eng. 2010;12:203–31.PubMedPubMedCentralCrossRefGoogle Scholar
  135. 135.
    Holst HI. Primary peripheral nerve repair in the hand and upper extremity. J Trauma. 1975;15:909–11.PubMedCrossRefGoogle Scholar
  136. 136.
    Holz A, Frank M, Copeland NG, Gilbert DJ, Jenkins NA, Schwab ME. Chromosomal localization of the myelin-associated oligodendrocytic basic protein and expression in the genetically linked neurological mouse mutants ducky and tippy. J Neurochem. 1997;69:1801–9.PubMedCrossRefGoogle Scholar
  137. 137.
    Holz A, Schwab ME. Developmental expression of the myelin gene MOBP in the rat nervous system. J Neurocytol. 1997;26:467–77.PubMedCrossRefGoogle Scholar
  138. 138.
    Hooker D. Studies on regeneration in the spinal cord. III. Reestablishment of anatomical and physiological continuity after transection in frog tadpoles. J Comp Neurol (Philadelphia). 1925;38:315–47; p [1 v.].CrossRefGoogle Scholar
  139. 139.
    Hooker D. Spinal-cord regeneration in the young rainbow fish, Lebistes reticulatus. Jour Comp Neur (Philadelphia). 1932;56(Hooker D):277–97. p [1 v.].CrossRefGoogle Scholar
  140. 140.
    Horner PJ, Gage FH. Regenerating the damaged central nervous system. Nature. 2000;407:963–70.PubMedCrossRefGoogle Scholar
  141. 141.
    Hossain-Ibrahim MK, Rezajooi K, Stallcup WB, Lieberman AR, Anderson PN. Analysis of axonal regeneration in the central and peripheral nervous systems of the NG2-deficient mouse. BMC Neurosci. 2007;8:80.PubMedPubMedCentralCrossRefGoogle Scholar
  142. 142.
    Houle JD, Reier PJ. Transplantation of fetal spinal cord tissue into the chronically injured adult rat spinal cord. J Comp Neurol. 1988;269:535–47.PubMedCrossRefGoogle Scholar
  143. 143.
    Huber AB, Schwab ME. Nogo-A, a potent inhibitor of neurite outgrowth and regeneration. Biol Chem. 2000;381:407–19.PubMedCrossRefGoogle Scholar
  144. 144.
    Hudson AR, Hunter D. Timing of peripheral nerve repair: important local neuropathological factors. Clin Neurosurg. 1977;24:391–405.PubMedGoogle Scholar
  145. 145.
    Hunanyan AS, Petrosyan HA, Alessi V, Arvanian VL. Combination of chondroitinase ABC and AAV-NT3 promotes neural plasticity at descending spinal pathways after thoracic contusion in rats. J Neurophysiol. 2013;110:1782–92.PubMedCrossRefGoogle Scholar
  146. 146.
    Hunt D, Mason MR, Campbell G, Coffin R, Anderson PN. Nogo receptor mRNA expression in intact and regenerating CNS neurons. Mol Cell Neurosci. 2002;20:537–52.PubMedCrossRefGoogle Scholar
  147. 147.
    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.PubMedCrossRefGoogle Scholar
  148. 148.
    Hunt D, Coffin RS, Prinjha RK, Campbell G, Anderson PN. Nogo-A expression in the intact and injured nervous system. Mol Cell Neurosci. 2003;24:1083–102.PubMedCrossRefGoogle Scholar
  149. 149.
    IJpma FF, Van De Graaf RC, Meek MF. The early history of tubulation in nerve repair. J Hand Surg Eur Vol. 2008;33:581–6.PubMedCrossRefGoogle Scholar
  150. 150.
    Ishikawa Y, Imagama S, Ohgomori T, Ishiguro N, Kadomatsu K. A combination of keratan sulfate digestion and rehabilitation promotes anatomical plasticity after rat spinal cord injury. Neurosci Lett. 2015;593:13–8.PubMedCrossRefGoogle Scholar
  151. 151.
    Ito Z, Sakamoto K, Imagama S, Matsuyama Y, Zhang H, Hirano K, Ando K, Yamashita T, Ishiguro N, Kadomatsu K. N-acetylglucosamine 6-O-sulfotransferase-1-deficient mice show better functional recovery after spinal cord injury. J Neurosci. 2010;30:5937–47.PubMedCrossRefGoogle Scholar
  152. 152.
    Jahan N, Hannila SS. Transforming growth factor beta-induced expression of chondroitin sulfate proteoglycans is mediated through non-Smad signaling pathways. Exp Neurol. 2015;263:372–84.PubMedCrossRefGoogle Scholar
  153. 153.
    Jenq CB, Jenq LL, Bear HM, Coggeshall RE. Conditioning lesions of peripheral nerves change regenerated axon numbers. Brain Res. 1988;457:63–9.PubMedCrossRefGoogle Scholar
  154. 154.
    Jin WL, Liu YY, Liu HL, Yang H, Wang Y, Jiao XY, Ju G. Intraneuronal localization of Nogo-A in the rat. J Comp Neurol. 2003;458:1–10.PubMedCrossRefGoogle Scholar
  155. 155.
    Jinek M, Chylinski K, Fonfara I, Hauer M, Doudna JA, Charpentier E. A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science. 2012;337:816–21.PubMedCrossRefGoogle Scholar
  156. 156.
    Johansson CB, Momma S, Clarke DL, Risling M, Lendahl U, Frisen J. Identification of a neural stem cell in the adult mammalian central nervous system. Cell. 1999;96:25–34.PubMedCrossRefGoogle Scholar
  157. 157.
    Jones LL, Yamaguchi Y, Stallcup WB, Tuszynski MH. 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
  158. 158.
    Jones LL, Sajed D, Tuszynski MH. Axonal regeneration through regions of chondroitin sulfate proteoglycan deposition after spinal cord injury: a balance of permissiveness and inhibition. J Neurosci. 2003;23:9276–88.PubMedGoogle Scholar
  159. 159.
    Jonsson S, Wiberg R, McGrath AM, Novikov LN, Wiberg M, Novikova LN, Kingham PJ. Effect of delayed peripheral nerve repair on nerve regeneration. Schwann cell function and target muscle recovery. PLoS ONE. 2013;8:e56484.PubMedPubMedCentralCrossRefGoogle Scholar
  160. 160.
    Josephson A, Trifunovski A, Scheele C, Widenfalk J, Wahlestedt C, Brene S, Olson L, Spenger C. Activity-induced and developmental downregulation of the Nogo receptor. Cell Tissue Res. 2003;311:333–42.PubMedGoogle Scholar
  161. 161.
    Joy MT, Vrbova G, Dhoot GK, Anderson PN. Sulf1 and Sulf2 expression in the nervous system and its role in limiting neurite outgrowth in vitro. Exp Neurol. 2015;263:150–60.PubMedCrossRefGoogle Scholar
  162. 162.
    Kaku M. Physics of the impossible: a scientific exploration into the world of phasers, force fields, teleportation, and time travel. 1st ed. New York: Doubleday; 2008.Google Scholar
  163. 163.
    Kalbermatten DF, Kingham PJ, Mahay D, Mantovani C, Pettersson J, Raffoul W, Balcin H, Pierer G, Terenghi G. Fibrin matrix for suspension of regenerative cells in an artificial nerve conduit. J Plast Reconstr Aesthet Surg. 2008;61:669–75.PubMedCrossRefGoogle Scholar
  164. 164.
    Kallioinen MJ, Heikkinen ER, Nystrom S. Histopathological and immunohistochemical changes in neurosurgically resected epileptic foci. Acta Neurochir (Wien). 1987;89:122–9.CrossRefGoogle Scholar
  165. 165.
    Kaneko A, Matsushita A, Sankai Y. A 3D nanofibrous hydrogel and collagen sponge scaffold promotes locomotor functional recovery, spinal repair, and neuronal regeneration after complete transection of the spinal cord in adult rats. Biomed Mater. 2015;10(1):015008.PubMedCrossRefGoogle Scholar
  166. 166.
    Kanno H, Pressman Y, Moody A, Berg R, Muir EM, Rogers JH, Ozawa H, Itoi E, Pearse DD, Bunge MB. Combination of engineered schwann cell grafts to secrete neurotrophin and chondroitinase promotes axonal regeneration and locomotion after spinal cord injury. J Neurosci. 2014;34:1838–55.PubMedPubMedCentralCrossRefGoogle Scholar
  167. 167.
    Kaplan HM, Mishra P, Kohn J. The overwhelming use of rat models in nerve regeneration research may compromise designs of nerve guidance conduits for humans. J Mater Sci Mater Med. 2015;26(8):226.PubMedPubMedCentralCrossRefGoogle Scholar
  168. 168.
    Karimi-Abdolrezaee S, Eftekharpour E, Wang J, Schut D, Fehlings MG. Synergistic effects of transplanted adult neural stem/progenitor cells, chondroitinase, and growth factors promote functional repair and plasticity of the chronically injured spinal cord. J Neurosci. 2010;30:1657–76.PubMedCrossRefGoogle Scholar
  169. 169.
    Karimi-Abdolrezaee S, Schut D, Wang J, Fehlings MG. Chondroitinase and growth factors enhance activation and oligodendrocyte differentiation of endogenous neural precursor cells after spinal cord injury. PLoS One. 2012;7:e37589.PubMedPubMedCentralCrossRefGoogle Scholar
  170. 170.
    Kartje GL, Schulz MK, Lopez-Yunez A, Schnell L, Schwab ME. Corticostriatal plasticity is restricted by myelin-associated neurite growth inhibitors in the adult rat. Ann Neurol. 1999;45:778–86.PubMedCrossRefGoogle Scholar
  171. 171.
    Kim JE, Bonilla IE, Qiu D, Strittmatter SM. Nogo-C is sufficient to delay nerve regeneration. Mol Cell Neurosci. 2003;23:451–9.PubMedCrossRefGoogle Scholar
  172. 172.
    Kim JE, Li S, GrandPre T, Qiu D, Strittmatter SM. Axon regeneration in young adult mice lacking Nogo-A/B. Neuron. 2003;38:187–99.PubMedCrossRefGoogle Scholar
  173. 173.
    Klapka N, Hermanns S, Straten G, Masanneck C, Duis S, Hamers FP, Muller D, Zuschratter W, Muller HW. Suppression of fibrous scarring in spinal cord injury of rat promotes long-distance regeneration of corticospinal tract axons, rescue of primary motoneurons in somatosensory cortex and significant functional recovery. Eur J Neurosci. 2005;22:3047–58.PubMedCrossRefGoogle Scholar
  174. 174.
    Kline DG, Hackett ER. Reappraisal of timing for exploration of civilian peripheral nerve injuries. Surgery. 1975;78:54–65.PubMedGoogle Scholar
  175. 175.
    Knikou M, Angeli CA, Ferreira CK, Harkema SJ. Flexion reflex modulation during stepping in human spinal cord injury. Exp Brain Res. 2009;196:341–51.PubMedCrossRefGoogle Scholar
  176. 176.
    Knikou M, Angeli CA, Ferreira CK, Harkema SJ. Soleus H-reflex modulation during body weight support treadmill walking in spinal cord intact and injured subjects. Exp Brain Res. 2009;193:397–407.PubMedCrossRefGoogle Scholar
  177. 177.
    Kose N, Muezzinoglu O, Bilgin S, Karahan S, Isikay I, Bilginer B. Early rehabilitation improves neurofunctional outcome after surgery in children with spinal tumors. Neural Regen Res. 2014;9:129–34.PubMedPubMedCentralCrossRefGoogle Scholar
  178. 178.
    Krautstrunk M, Scholtes F, Martin D, Schoenen J, Schmitt AB, Plate D, Nacimiento W, Noth J, Brook GA. Increased expression of the putative axon growth-repulsive extracellular matrix molecule, keratan sulphate proteoglycan, following traumatic injury of the adult rat spinal cord. Acta Neuropathol. 2002;104:592–600.PubMedGoogle Scholar
  179. 179.
    Kuiken TA, Dumanian GA, Lipschutz RD, Miller LA, Stubblefield KA. The use of targeted muscle reinnervation for improved myoelectric prosthesis control in a bilateral shoulder disarticulation amputee. Prosthet Orthot Int. 2004;28:245–53.PubMedGoogle Scholar
  180. 180.
    Kuiken TA, Miller LA, Lipschutz RD, Lock BA, Stubblefield K, Marasco PD, Zhou P, Dumanian GA. Targeted reinnervation for enhanced prosthetic arm function in a woman with a proximal amputation: a case study. Lancet. 2007;369:371–80.PubMedCrossRefGoogle Scholar
  181. 181.
    Kumar P, Choonara YE, Modi G, Naidoo D, Pillay V. Multifunctional therapeutic delivery strategies for effective neuro-regeneration following traumatic spinal cord injury. Curr Pharm Des. 2015;21:1517–28.PubMedCrossRefGoogle Scholar
  182. 182.
    Lang DM, Rubin BP, Schwab ME, Stuermer CA. CNS myelin and oligodendrocytes of the Xenopus spinal cord – but not optic nerve – are nonpermissive for axon growth. J Neurosci. 1995;15:99–109.PubMedGoogle Scholar
  183. 183.
    Lang BT, Cregg JM, DePaul MA, Tran AP, Xu K, Dyck SM, Madalena KM, Brown BP, Weng YL, Li S, Karimi-Abdolrezaee S, Busch SA, Shen Y, Silver J. Modulation of the proteoglycan receptor PTPsigma promotes recovery after spinal cord injury. Nature. 2015;518:404–8.PubMedCrossRefGoogle Scholar
  184. 184.
    Lankford KL, Waxman SG, Kocsis JD. Mechanisms of enhancement of neurite regeneration in vitro following a conditioning sciatic nerve lesion. J Comp Neurol. 1998;391:11–29.PubMedPubMedCentralCrossRefGoogle Scholar
  185. 185.
    Lau LW, Keough MB, Haylock-Jacobs S, Cua R, Doring A, Sloka S, Stirling DP, Rivest S, Yong VW. Chondroitin sulfate proteoglycans in demyelinated lesions impair remyelination. Ann Neurol. 2012;72:419–32.PubMedCrossRefGoogle Scholar
  186. 186.
    Lauren J, Airaksinen MS, Saarma M, Timmusk T. Two novel mammalian Nogo receptor homologs differentially expressed in the central and peripheral nervous systems. Mol Cell Neurosci. 2003;24:581–94.PubMedCrossRefGoogle Scholar
  187. 187.
    Lazar DA, Ellegala DB, Avellino AM, Dailey AT, Andrus K, Kliot M. Modulation of macrophage and microglial responses to axonal injury in the peripheral and central nervous systems. Neurosurgery. 1999;45:593–600.PubMedCrossRefGoogle Scholar
  188. 188.
    Ledford H. CRISPR, the disruptor. News feature. Nature. 2015;522:20–4.PubMedCrossRefGoogle Scholar
  189. 189.
    Lee H, McKeon RJ, Bellamkonda RV. Sustained delivery of thermostabilized chABC enhances axonal sprouting and functional recovery after spinal cord injury. Proc Natl Acad Sci U S A. 2010;107:3340–5.PubMedCrossRefGoogle Scholar
  190. 190.
    Lee JK, Geoffroy CG, Chan AF, Tolentino KE, Crawford MJ, Leal MA, Kang B, Zheng B. Assessing spinal axon regeneration and sprouting in Nogo-, MAG-, and OMgp-deficient mice. Neuron. 2010;66:663–70.PubMedPubMedCentralCrossRefGoogle Scholar
  191. 191.
    Levine JM. Increased expression of the NG2 chondroitin-sulfate proteoglycan after brain injury. J Neurosci. 1994;14:4716–30.PubMedGoogle Scholar
  192. 192.
    Lewis PM, Ackland HM, Lowery AJ, Rosenfeld JV. Restoration of vision in blind individuals using bionic devices: a review with a focus on cortical visual prostheses. Brain Res. 2015;1595:51–73.PubMedCrossRefGoogle Scholar
  193. 193.
    Li S, Strittmatter SM. Delayed systemic Nogo-66 receptor antagonist promotes recovery from spinal cord injury. J Neurosci. 2003;23:4219–27.PubMedGoogle Scholar
  194. 194.
    Li SX, Kim JE, Liu BP, Li MW, Ji BX, Pepinsky B, Relton J, Strittmatter SM. Inhibition of Nogo-66 receptor with its soluble ectodomain promotes axonal regeneration and functional recovery after spinal cord injury. J Neurotrauma. 2003;20:1057.Google Scholar
  195. 195.
    Li ZW, Li JJ, Wang L, Zhang JP, Wu JJ, Mao XQ, Shi GF, Wang Q, Wang F, Zou J. Epidermal growth factor receptor inhibitor ameliorates excessive astrogliosis and improves the regeneration microenvironment and functional recovery in adult rats following spinal cord injury. J Neuroinflammation. 2014;11:71.PubMedPubMedCentralCrossRefGoogle Scholar
  196. 196.
    Liebscher T, Schnell L, Schnell D, Scholl J, Schneider R, Gullo M, Fouad K, Mir A, Rausch M, Kindler D, Hamers FP, Schwab ME. Nogo-A antibody improves regeneration and locomotion of spinal cord-injured rats. Ann Neurol. 2005;58:706–19.PubMedCrossRefGoogle Scholar
  197. 197.
    Liu Y, Himes BT, Moul J, Huang W, Chow SY, Tessler A, Fischer I. Application of recombinant adenovirus for in vivo gene delivery to spinal cord. Brain Res. 1997;768:19–29.PubMedCrossRefGoogle Scholar
  198. 198.
    Liu S, Peulve P, Jin O, Boisset N, Tiollier J, Said G, Tadie M. Axonal regrowth through collagen tubes bridging the spinal cord to nerve roots. J Neurosci Res. 1997;49:425–32.PubMedCrossRefGoogle Scholar
  199. 199.
    Liu YY, Jin WL, Liu HL, Ju G. Electron microscopic localization of Nogo-A at the postsynaptic active zone of the rat. Neurosci Lett. 2003;346:153–6.PubMedCrossRefGoogle Scholar
  200. 200.
    Liu K, Lu Y, Lee JK, Samara R, Willenberg R, Sears-Kraxberger I, Tedeschi A, Park KK, Jin D, Cai B, Xu B, Connolly L, Steward O, Zheng B, He Z. PTEN deletion enhances the regenerative ability of adult corticospinal neurons. Nat Neurosci. 2010;13:1075–81.PubMedPubMedCentralCrossRefGoogle Scholar
  201. 201.
    Loeb GE. We made the deaf hear. Now what? In: Berger TW, Glanzman DL, editors. Toward replacement parts for the brain: implantable biomimetic electronics as neural prostheses. Cambridge: MIT Press; 2005. p. 3–13.Google Scholar
  202. 202.
    Loeb GE. Neuroprosthetic interfaces – The reality behind bionics and cyborgs. In: Schleidgen S, Jungert M, Bauer R, Sandow V, editors. Human nature and self-design. Paderborn, Germany: Mentis Verlag GmbH; 2011.Google Scholar
  203. 203.
    Loeb GE, Zhou L, Zheng K, Nicholson A, Peck RA, Krishnan A, Silka M, Pruetz J, Chmait R, Bar-Cohen Y. Design and testing of a percutaneously implantable fetal pacemaker. Ann Biomed Eng. 2013;41:17–27.PubMedCrossRefGoogle Scholar
  204. 204.
    de Nó Lorente R. La regeneración de la medula espinal en las larvas de batracio. Trab Lab Invest Biol Univ Madrid. 1921;19:147–83.Google Scholar
  205. 205.
    Lu P, Jones LL, Tuszynski MH. Axon regeneration through scars and into sites of chronic spinal cord injury. Exp Neurol. 2007;203:8–21.PubMedCrossRefGoogle Scholar
  206. 206.
    Lu P, Tuszynski MH. Growth factors and combinatorial therapies for CNS regeneration. Exp Neurol. 2008;209:313–20.PubMedCrossRefGoogle Scholar
  207. 207.
    Lu P, Wang Y, Graham L, McHale K, Gao M, Wu D, Brock J, Blesch A, Rosenzweig ES, Havton LA, Zheng B, Conner JM, Marsala M, Tuszynski MH. Long-distance growth and connectivity of neural stem cells after severe spinal cord injury. Cell. 2012;150:1264–73.PubMedPubMedCentralCrossRefGoogle Scholar
  208. 208.
    Lu P, Blesch A, Graham L, Wang Y, Samara R, Banos K, Haringer V, Havton L, Weishaupt N, Bennett D, Fouad K, Tuszynski MH. Motor axonal regeneration after partial and complete spinal cord transection. J Neurosci. 2012;32:8208–18.PubMedPubMedCentralCrossRefGoogle Scholar
  209. 209.
    Lu P, Woodruff G, Wang Y, Graham L, Hunt M, Wu D, Boehle E, Ahmad R, Poplawski G, Brock J, Goldstein LS, Tuszynski MH. Long-distance axonal growth from human induced pluripotent stem cells after spinal cord injury. Neuron. 2014;83:789–96.PubMedPubMedCentralCrossRefGoogle Scholar
  210. 210.
    MacCreight J. The regeneration of the spinal cord in adult Triturus viridescens. Univ Pittsburgh Bull. 1931;28:7.Google Scholar
  211. 211.
    Maier IC, Ichiyama RM, Courtine G, Schnell L, Lavrov I, Edgerton VR, Schwab ME. Differential effects of anti-Nogo-A antibody treatment and treadmill training in rats with incomplete spinal cord injury. Brain. 2009;132:1426–40.PubMedCrossRefGoogle Scholar
  212. 212.
    Mansour H, Asher R, Dahl D, Labkovsky B, Perides G, Bignami A. Permissive and non-permissive reactive astrocytes: immunofluorescence study with antibodies to the glial hyaluronate-binding protein. J Neurosci Res. 1990;25:300–11.PubMedCrossRefGoogle Scholar
  213. 213.
    Markets and Markets Report. Nerve repair & regeneration market by xenografts (conduits, protectors), neuromodulation [internal (spinal cord, deep brain), external (transcranial magnetic)], surgery [direct nerve repair, grafting, stem cell] – Global trend & forecast to 2018. By: marketsandmarkets.com. Report Code: BT 2105. Sep 2013.Google Scholar
  214. 214.
    Matsui F, Oohira A. Proteoglycans and injury of the central nervous system. Congenit Anom (Kyoto). 2004;44:181–8.CrossRefGoogle Scholar
  215. 215.
    Matthews MA, St Onge MF, Faciane CL, Gelderd JB. Axon sprouting into segments of rat spinal cord adjacent to the site of a previous transection. Neuropathol Appl Neurobiol. 1979;5:181–96.PubMedCrossRefGoogle Scholar
  216. 216.
    McAllister RM, Gilbert SE, Calder JS, Smith PJ. The epidemiology and management of upper limb peripheral nerve injuries in modern practice. J Hand Surg Br. 1996;21:4–13.PubMedCrossRefGoogle Scholar
  217. 217.
    McEvoy RC, Leung PE. Transplantation of fetal rat islets into the cerebral ventricles of alloxan-diabetic rats. Amelioration of diabetes by syngeneic but not allogeneic islets. Diabetes. 1983;32:852–7.PubMedCrossRefGoogle Scholar
  218. 218.
    McGee AW, Strittmatter SM. The Nogo-66 receptor: focusing myelin inhibition of axon regeneration. Trends Neurosci. 2003;26:193–8.PubMedCrossRefGoogle Scholar
  219. 219.
    McKay WB, Ovechkin AV, Vitaz TW, Terson de Paleville DG, Harkema SJ. Long-lasting involuntary motor activity after spinal cord injury. Spinal Cord. 2011;49:87–93.PubMedCrossRefGoogle Scholar
  220. 220.
    McKeon RJ, Schreiber RC, Rudge JS, Silver J. 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
  221. 221.
    Mehta NR, Lopez PH, Vyas AA, Schnaar RL. Gangliosides and Nogo receptors independently mediate myelin-associated glycoprotein inhibition of neurite outgrowth in different nerve cells. J Biol Chem. 2007;282:27875–86.PubMedPubMedCentralCrossRefGoogle Scholar
  222. 222.
    Meier S, Brauer AU, Heimrich B, Schwab ME, Nitsch R, Savaskan NE. Molecular analysis of Nogo expression in the hippocampus during development and following lesion and seizure. FASEB J. 2003;17:1153–5.PubMedCrossRefGoogle Scholar
  223. 223.
    Merzenich MM, Kaas JH, Wall J, Nelson RJ, Sur M, Felleman D. Topographic reorganization of somato-sensory cortical areas 3B and 1 in adult monkeys following restricted deafferentation. Neuroscience. 1983;8:33–55.PubMedCrossRefGoogle Scholar
  224. 224.
    Miao QL, Ye Q, Zhang XH. Perineuronal net, CSPG receptor and their regulation of neural plasticity. Sheng Li Xue Bao. 2014;66:387–97.PubMedGoogle Scholar
  225. 225.
    Midha R, Munro CA, Chan S, Nitising A, Xu QG, Gordon T. Regeneration into protected and chronically denervated peripheral nerve stumps. Neurosurgery. 2005;57:1289–99.PubMedCrossRefGoogle Scholar
  226. 226.
    Milbreta U, von Boxberg Y, Mailly P, Nothias F, Soares S. Astrocytic and vascular remodeling in the injured adult rat spinal cord after chondroitinase ABC treatment. J Neurotrauma. 2014;31:803–18.PubMedPubMedCentralCrossRefGoogle Scholar
  227. 227.
    Miller S, Scott PD. A model of the spinal locomotor generator in the cat [proceedings]. J Physiol. 1977;269:20P–2.PubMedGoogle Scholar
  228. 228.
    Miller S, Scott PD. The spinal locomotor generator. Exp Brain Res. 1977;30:387–403.PubMedGoogle Scholar
  229. 229.
    Ming GL, Song HJ, Berninger B, Holt CE, Tessier-Lavigne M, Poo MM. cAMP-dependent growth cone guidance by netrin-1. Neuron. 1997;19:1225–35.PubMedCrossRefGoogle Scholar
  230. 230.
    Mohney G. Doctor aims to perform head transplant in 2017, Experts remain skeptical. ABC News post. 2015. Retrieved Dec 22, 2015, from: http://abcnews.go.com/Health/doctor-aims-perform-head-transplant-2017-experts-remain/story?id=33775323.
  231. 231.
    Mohseni MA, Pour JS, Pour JG. Primary and delayed repair and nerve grafting for treatment of cut median and ulnar nerves. Pak J Biol Sci. 2010;13:287–92.PubMedCrossRefGoogle Scholar
  232. 232.
    Mondello SE, Jefferson SC, Tester NJ, Howland DR. Impact of treatment duration and lesion size on effectiveness of chondroitinase treatment post-SCI. Exp Neurol. 2015;267:64–77.PubMedCrossRefGoogle Scholar
  233. 233.
    Mullner A, Gonzenbach RR, Weinmann O, Schnell L, Liebscher T, Schwab ME. Lamina-specific restoration of serotonergic projections after Nogo-A antibody treatment of spinal cord injury in rats. Eur J Neurosci. 2008;27:326–33.PubMedCrossRefGoogle Scholar
  234. 234.
    Nakamae T, Tanaka N, Nakanishi K, Kamei N, Sasaki H, Hamasaki T, Yamada K, Yamamoto R, Mochizuki Y, Ochi M. Chondroitinase ABC promotes corticospinal axon growth in organotypic cocultures. Spinal Cord. 2009;47:161–5.PubMedCrossRefGoogle Scholar
  235. 235.
    Nakamae T, Tanaka N, Nakanishi K, Kamei N, Sasaki H, Hamasaki T, Yamada K, Yamamoto R, Izumi B, Ochi M. The effects of combining chondroitinase ABC and NEP1-40 on the corticospinal axon growth in organotypic co-cultures. Neurosci Lett. 2010;476:14–7.PubMedCrossRefGoogle Scholar
  236. 236.
    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.PubMedCrossRefGoogle Scholar
  237. 237.
    Neumann S, Bradke F, Tessier-Lavigne M, Basbaum AI. Regeneration of sensory axons within the injured spinal cord induced by intraganglionic cAMP elevation. Neuron. 2002;34:885–93.PubMedCrossRefGoogle Scholar
  238. 238.
    Neumann S, Skinner K, Basbaum AI. Sustaining intrinsic growth capacity of adult neurons promotes spinal cord regeneration. Proc Natl Acad Sci U S A. 2005;102:16848–52.PubMedPubMedCentralCrossRefGoogle Scholar
  239. 239.
    Nghiem BT, Sando IC, Gillespie RB, McLaughlin BL, Gerling GJ, Langhals NB, Urbanchek MG, Cederna PS. Providing a sense of touch to prosthetic hands. Plast Reconstr Surg. 2015;135:1652–63.PubMedCrossRefGoogle Scholar
  240. 240.
    Nie DY, Zhou ZH, Ang BT, Teng FY, Xu G, Xiang T, Wang CY, Zeng L, Takeda Y, Xu TL, Ng YK, Faivre-Sarrailh C, Popko B, Ling EA, Schachner M, Watanabe K, Pallen CJ, Tang BL, Xiao ZC. Nogo-A at CNS paranodes is a ligand of Caspr: possible regulation of K(+) channel localization. EMBO J. 2003;22:5666–78.PubMedPubMedCentralCrossRefGoogle Scholar
  241. 241.
    Niederost BP, Zimmermann DR, Schwab ME, Bandtlow CE. Bovine CNS myelin contains neurite growth-inhibitory activity associated with chondroitin sulfate proteoglycans. J Neurosci. 1999;19:8979–89.PubMedGoogle Scholar
  242. 242.
    Novikova L, Novikov L, Kellerth JO. Effects of neurotransplants and BDNF on the survival and regeneration of injured adult spinal motoneurons. Eur J Neurosci. 1997;9:2774–7.PubMedCrossRefGoogle Scholar
  243. 243.
    Oblinger MM, Lasek RJ. A conditioning lesion of the peripheral axons of dorsal root ganglion cells accelerates regeneration of only their peripheral axons. J Neurosci. 1984;4:1736–44.PubMedGoogle Scholar
  244. 244.
    Oertle T, van der Haar ME, Bandtlow CE, Robeva A, Burfeind P, Buss A, Huber AB, Simonen M, Schnell L, Brosamle C, Kaupmann K, Vallon R, Schwab ME. Nogo-A inhibits neurite outgrowth and cell spreading with three discrete regions. J Neurosci. 2003;23:5393–406.PubMedGoogle Scholar
  245. 245.
    Orlando C, Raineteau O. Integrity of cortical perineuronal nets influences corticospinal tract plasticity after spinal cord injury. Brain Struct Funct. 2015;220(2):1077–91.PubMedCrossRefGoogle Scholar
  246. 246.
    Orlando C, Raineteau O. Integrity of cortical perineuronal nets influences corticospinal tract plasticity after spinal cord injury. Brain Struct Funct. 2015;220:1077–91.PubMedCrossRefGoogle Scholar
  247. 247.
    Oudega M, Xu XM, Guenard V, Kleitman N, Bunge MB. A combination of insulin-like growth factor-I and platelet-derived growth factor enhances myelination but diminishes axonal regeneration into Schwann cell grafts in the adult rat spinal cord. Glia. 1997;19:247–58.PubMedCrossRefGoogle Scholar
  248. 248.
    Pabari A, Lloyd-Hughes H, Seifalian AM, Mosahebi A. Nerve conduits for peripheral nerve surgery. Plast Reconstr Surg. 2014;133:1420–30.PubMedCrossRefGoogle Scholar
  249. 249.
    Pei Y, Dong S, Roth BL. Generation of designer receptors exclusively activated by designer drugs (DREADDs) using directed molecular evolution. Curr Protoc Neurosci. 2010;Chapter 4:Unit 4.33.PubMedGoogle Scholar
  250. 250.
    Pellegrino RG, Spencer PS. Schwann cell mitosis in response to regenerating peripheral axons in vivo. Brain Res. 1985;341:16–25.PubMedCrossRefGoogle Scholar
  251. 251.
    Pettersson J, Kalbermatten D, Mcgrath A, Novikova LN. Biodegradable fibrin conduit promotes long-term regeneration after peripheral nerve injury in adult rats. J Plast Reconstr Aesthet Surg. 2010;63:1893–9.PubMedCrossRefGoogle Scholar
  252. 252.
    Pignot V, Hein AE, Barske C, Wiessner C, Walmsley AR, Kaupmann K, Mayeur H, Sommer B, Mir AK, Frentzel S. Characterization of two novel proteins, NgRH1 and NgRH2, structurally and biochemically homologous to the Nogo-66 receptor. J Neurochem. 2003;85:717–28.PubMedCrossRefGoogle Scholar
  253. 253.
    Piskin A, Altunkaynak BZ, Citlak A, Sezgin H, Yaziotaciota O, Kaplan S. Immediate versus delayed primary nerve repair in the rabbit sciatic nerve. Neural Regen Res. 2013;8:3410–5.PubMedPubMedCentralGoogle Scholar
  254. 254.
    Possover M. Recovery of sensory and supraspinal control of leg movement in people with chronic paraplegia: a case series. Arch Phys Med Rehabil. 2014;95:610–4.PubMedCrossRefGoogle Scholar
  255. 255.
    Pot C, Simonen M, Weinmann O, Schnell L, Christ F, Stoeckle S, Berger P, Rulicke T, Suter U, Schwab ME. Nogo-A expressed in Schwann cells impairs axonal regeneration after peripheral nerve injury. J Cell Biol. 2002;159:29–35.PubMedPubMedCentralCrossRefGoogle Scholar
  256. 256.
    Prendergast J, Stelzner DJ. Increases in collateral axonal growth rostral to a thoracic hemisection in neonatal and weanling rat. J Comp Neurol. 1976;166:145–61.PubMedCrossRefGoogle Scholar
  257. 257.
    Prendergast J, Stelzner DJ. Changes in the magnocellular portion of the red nucleus following thoracic hemisection in the neonatal and adult rat. J Comp Neurol. 1976;166:163–71.PubMedCrossRefGoogle Scholar
  258. 258.
    Qi B, Qi Y, Watari A, Yoshioka N, Inoue H, Minemoto Y, Yamashita K, Sasagawa T, Yutsudo M. Pro-apoptotic ASY/Nogo-B protein associates with ASYIP. J Cell Physiol. 2003;196:312–8.PubMedCrossRefGoogle Scholar
  259. 259.
    Qiao J, Huang F, Lum H. PKA inhibits RhoA activation: a protection mechanism against endothelial barrier dysfunction. Am J Physiol Lung Cell Mol Physiol. 2003;284:L972–80.PubMedCrossRefGoogle Scholar
  260. 260.
    Qiu J, Cafferty WB, McMahon SB, Thompson SW. Conditioning injury-induced spinal axon regeneration requires signal transducer and activator of transcription 3 activation. J Neurosci. 2005;25:1645–53.PubMedCrossRefGoogle Scholar
  261. 261.
    Raineteau O, Z’Graggen WJ, Thallmair M, Schwab ME. Sprouting and regeneration after pyramidotomy and blockade of the myelin-associated neurite growth inhibitors NI 35/250 in adult rats. Eur J Neurosci. 1999;11:1486–90.PubMedCrossRefGoogle Scholar
  262. 262.
    Ramón y Cajal S. Notas preventivas sobre la degeneración y regeneración de las vías nerviosas centrales. Trab Lab Invest Biol Univ Madrid. 1906;4:295–301.Google Scholar
  263. 263.
    RamónyCajal S. Degeneration and regeneration of the nervous system. London: Oxford Univ. Press; 1928.Google Scholar
  264. 264.
    Reier PJ. Penetration of grafted astrocytic scars by regenerating optic nerve axons in Xenopus tadpoles. Brain Res. 1979;164:61–8.PubMedCrossRefGoogle Scholar
  265. 265.
    Reier PJ, Perlow MJ, Guth L. Development of embryonic spinal cord transplants in the rat. Brain Res. 1983;312:201–19.PubMedCrossRefGoogle Scholar
  266. 266.
    Reier PJ. Neural tissue grafts and repair of the injured spinal cord. Neuropathol Appl Neurobiol. 1985;11:81–104.PubMedCrossRefGoogle Scholar
  267. 267.
    Reier PJ, Bregman BS, Wujek JR. Intraspinal transplantation of embryonic spinal cord tissue in neonatal and adult rats. J Comp Neurol. 1986;247:275–96.PubMedCrossRefGoogle Scholar
  268. 268.
    Reier PJ, Houle JD. The glial scar: its bearing on axonal elongation and transplantation approaches to CNS repair. Adv Neurol. 1988;47:87–138.PubMedGoogle Scholar
  269. 269.
    Risling M, Linda H, Cullheim S, Franson P. A persistent defect in the blood–brain barrier after ventral funiculus lesion in adult cats: implications for CNS regeneration? Brain Res. 1989;494:13–21.PubMedCrossRefGoogle Scholar
  270. 270.
    Ronkko H, Goransson H, Siironen P, Taskinen HS, Vuorinen V, Roytta M. The capacity of the distal stump of peripheral nerve to receive growing axons after two and six months denervation. Scand J Surg. 2011;100:223–9.PubMedCrossRefGoogle Scholar
  271. 271.
    Roy RR, Harkema SJ, Edgerton VR. Basic concepts of activity-based interventions for improved recovery of motor function after spinal cord injury. Arch Phys Med Rehabil. 2012;93:1487–97.PubMedCrossRefGoogle Scholar
  272. 272.
    Rubin BP, Spillmann AA, Bandtlow CE, Hillenbrand R, Keller F, Schwab ME. Inhibition of PC12 cell attachment and neurite outgrowth by detergent solubilized CNS myelin proteins. Eur J Neurosci. 1995;7:2524–9.PubMedCrossRefGoogle Scholar
  273. 273.
    Rudge JS, Silver J. Inhibition of neurite outgrowth on astroglial scars in vitro. J Neurosci. 1990;10:3594–603.PubMedGoogle Scholar
  274. 274.
    Sandrow-Feinberg HR, Houle JD. Exercise after spinal cord injury as an agent for neuroprotection, regeneration and rehabilitation. Brain Res. 1619;2015:12–21.Google Scholar
  275. 275.
    Sapieha PS, Duplan L, Uetani N, Joly S, Tremblay ML, Kennedy TE, Di Polo A. Receptor protein tyrosine phosphatase sigma inhibits axon regrowth in the adult injured CNS. Mol Cell Neurosci. 2005;28:625–35.PubMedCrossRefGoogle Scholar
  276. 276.
    Sato KL, Johanek LM, Sanada LS, Sluka KA. Spinal cord stimulation reduces mechanical hyperalgesia and glial cell activation in animals with neuropathic pain. Anesth Analg. 2014;118:464–72.PubMedPubMedCentralCrossRefGoogle Scholar
  277. 277.
    Savio T, Schwab ME. Lesioned corticospinal tract axons regenerate in myelin-free rat spinal cord. Proc Natl Acad Sci U S A. 1990;87:4130–3.PubMedPubMedCentralCrossRefGoogle Scholar
  278. 278.
    Sayenko DG, Angeli C, Harkema SJ, Edgerton VR, Gerasimenko YP. Neuromodulation of evoked muscle potentials induced by epidural spinal-cord stimulation in paralyzed individuals. J Neurophysiol. 2014;111:1088–99.PubMedCrossRefGoogle Scholar
  279. 279.
    Sceats Jr DJ, Friedman WA, Sypert GW, Ballinger Jr WE. Regeneration in peripheral nerve grafts to the cat spinal cord. Brain Res. 1986;362:149–56.PubMedCrossRefGoogle Scholar
  280. 280.
    Schaeren-Wiemers N, Schaefer C, Valenzuela DM, Yancopoulos GD, Schwab ME. Identification of new oligodendrocyte- and myelin-specific genes by a differential screening approach. J Neurochem. 1995;65:10–22.PubMedCrossRefGoogle Scholar
  281. 281.
    Schiefferdecker P. Ueber Regeneration, Degeneration und Architectur des Rèuckenmarkes. Berlin: Gedruckt bei G. Reimer; 1876. p. 76.Google Scholar
  282. 282.
    Schmidt CE, Leach JB. Neural tissue engineering: strategies for repair and regeneration. Annu Rev Biomed Eng. 2003;5:293–347.PubMedCrossRefGoogle Scholar
  283. 283.
    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.PubMedCrossRefGoogle Scholar
  284. 284.
    Schnell L, Schneider R, Kolbeck R, Barde YA, Schwab ME. Neurotrophin-3 enhances sprouting of corticospinal tract during development and after adult spinal cord lesion. Nature. 1994;367:170–3.PubMedCrossRefGoogle Scholar
  285. 285.
    Schnell L, Hunanyan AS, Bowers WJ, Horner PJ, Federoff HJ, Gullo M, Schwab ME, Mendell LM, Arvanian VL. Combined delivery of Nogo-A antibody, neurotrophin-3 and the NMDA-NR2d subunit establishes a functional ‘detour’ in the hemisected spinal cord. Eur J Neurosci. 2011;34:1256–67.PubMedPubMedCentralCrossRefGoogle Scholar
  286. 286.
    Schreyer DJ, Jones EG. Growing corticospinal axons by-pass lesions of neonatal rat spinal cord. Neuroscience. 1983;9:31–40.PubMedCrossRefGoogle Scholar
  287. 287.
    Schulz MK, Schnell L, Castro AJ, Schwab ME, Kartje GL. Cholinergic innervation of fetal neocortical transplants is increased after neutralization of myelin-associated neurite growth inhibitors. Exp Neurol. 1998;149:390–7.PubMedCrossRefGoogle Scholar
  288. 288.
    Schwab ME. Myelin-associated inhibitors of neurite growth and regeneration in the CNS. Trends Neurosci. 1990;13:452–6.PubMedCrossRefGoogle Scholar
  289. 289.
    Schwab ME, Schnell L. Channeling of developing rat corticospinal tract axons by myelin-associated neurite growth inhibitors. J Neurosci. 1991;11:709–21.PubMedGoogle Scholar
  290. 290.
    Schwab ME. Regeneration of lesioned CNS axons by neutralization of neurite growth inhibitors: a short review. J Neurotrauma. 1992;9 Suppl 1:S219–21.PubMedGoogle Scholar
  291. 291.
    Schwab ME, Bartholdi D. Degeneration and regeneration of axons in the lesioned spinal cord. Physiol Rev. 1996;76:319–70.PubMedGoogle Scholar
  292. 292.
    Schwab ME. Structural plasticity of the adult CNS. Negative control by neurite growth inhibitory signals. Int J Dev Neurosci. 1996;14:379–85.PubMedCrossRefGoogle Scholar
  293. 293.
    Schwab ME, Brosamle C. Regeneration of lesioned corticospinal tract fibers in the adult rat spinal cord under experimental conditions. Spinal Cord. 1997;35:469–73.PubMedCrossRefGoogle Scholar
  294. 294.
    Schwab ME, Strittmatter SM. Nogo limits neural plasticity and recovery from injury. Curr Opin Neurobiol. 2014;27:53–60.PubMedCrossRefGoogle Scholar
  295. 295.
    Schwegler G, Schwab ME, Kapfhammer JP. Increased collateral sprouting of primary afferents in the myelin-free spinal cord. J Neurosci. 1995;15:2756–67.PubMedGoogle Scholar
  296. 296.
    Seijffers R, Allchorne AJ, Woolf CJ. The transcription factor ATF-3 promotes neurite outgrowth. Mol Cell Neurosci. 2006;32:143–54.PubMedCrossRefGoogle Scholar
  297. 297.
    Seijffers R, Mills CD, Woolf CJ. ATF3 increases the intrinsic growth state of DRG neurons to enhance peripheral nerve regeneration. J Neurosci. 2007;27:7911–20.PubMedCrossRefGoogle Scholar
  298. 298.
    Sharpe AN, Jackson A. Upper-limb muscle responses to epidural, subdural and intraspinal stimulation of the cervical spinal cord. J Neural Eng. 2014;11:016005.PubMedPubMedCentralCrossRefGoogle Scholar
  299. 299.
    Sicotte M, Tsatas O, Jeong SY, Cai CQ, He Z, David S. 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.PubMedCrossRefGoogle Scholar
  300. 300.
    Siegel CS, Fink KL, Strittmatter SM, Cafferty WB. Plasticity of intact rubral projections mediates spontaneous recovery of function after corticospinal tract injury. J Neurosci. 2015;35:1443–57.PubMedPubMedCentralCrossRefGoogle Scholar
  301. 301.
    Simonen M, Pedersen V, Weinmann O, Schnell L, Buss A, Ledermann B, Christ F, Sansig G, van der Putten H, Schwab ME. Systemic deletion of the myelin-associated outgrowth inhibitor Nogo-A improves regenerative and plastic responses after spinal cord injury. Neuron. 2003;38:201–11.PubMedCrossRefGoogle Scholar
  302. 302.
    Smith GM, Miller RH, Silver J. Changing role of forebrain astrocytes during development, regenerative failure, and induced regeneration upon transplantation. J Comp Neurol. 1986;251:23–43.PubMedCrossRefGoogle Scholar
  303. 303.
    Smith GM, Strunz C. Growth factor and cytokine regulation of chondroitin sulfate proteoglycans by astrocytes. Glia. 2005;52:209–18.PubMedCrossRefGoogle Scholar
  304. 304.
    Song HJ, Ming GL, Poo MM. cAMP-induced switching in turning direction of nerve growth cones. Nature. 1997;388:275–9.PubMedCrossRefGoogle Scholar
  305. 305.
    Spejo AB, Oliveira AL. Synaptic rearrangement following axonal injury: old and new players. Neuropharmacology. 2015;96:113–23.PubMedCrossRefGoogle Scholar
  306. 306.
    Spillmann AA, Bandtlow CE, Lottspeich F, Keller F, Schwab ME. Identification and characterization of a bovine neurite growth inhibitor (bNI-220). J Biol Chem. 1998;273:19283–93.PubMedCrossRefGoogle Scholar
  307. 307.
    Starkey ML, Bartus K, Barritt AW, Bradbury EJ.Chondroitinase ABC promotes compensatory sprouting of the intact corticospinal tract and recovery of forelimb function following unilateral pyramidotomy in adult mice. Eur J Neurosci. 2012;36:3665–78.PubMedPubMedCentralCrossRefGoogle Scholar
  308. 308.
    Stocco A, Prat CS, Losey DM, Cronin JA, Wu J, Abernethy JA, et al. Playing 20 Questions with the mind: Collaborative problem solving by humans using a Brain-to-Brain Interface. PLoS One. 2015;10:e0137303.PubMedPubMedCentralCrossRefGoogle Scholar
  309. 309.
    Su H, Yuan Q, Qin D, Yang X, Wong WM, So KF, Wu W. Lithium enhances axonal regeneration in peripheral nerve by inhibiting glycogen synthase kinase 3beta activation. Biomed Res Int. 2014;2014:658753.PubMedPubMedCentralGoogle Scholar
  310. 310.
    Sugar O, Gerard RW. Spinal cord regeneration in the rat. J Neurophysiol. 1940;3:1–19.Google Scholar
  311. 311.
    Sutendra G, Dromparis P, Wright P, Bonnet S, Haromy A, Hao Z, McMurtry MS, Michalak M, Vance JE, Sessa WC, Michelakis ED. The role of Nogo and the mitochondria-endoplasmic reticulum unit in pulmonary hypertension. Sci Transl Med. 2011;3:88ra55.PubMedPubMedCentralCrossRefGoogle Scholar
  312. 312.
    Szynkaruk M, Kemp SW, Wood MD, Gordon T, Borschel GH. Experimental and clinical evidence for use of decellularized nerve allografts in peripheral nerve gap reconstruction. Tissue Eng Part B Rev. 2013;19:83–96.PubMedCrossRefGoogle Scholar
  313. 313.
    Tatagiba M, Brosamle C, Schwab ME. Regeneration of injured axons in the adult mammalian central nervous system. Neurosurgery. 1997;40:541–7.PubMedGoogle Scholar
  314. 314.
    Tator CH, Rivlin AS. Elimination of root regeneration in studies of spinal cord regeneration. Surg Neurol. 1983;19:255–9.PubMedCrossRefGoogle Scholar
  315. 315.
    Taylor GI, Ham FJ. The free vascularized nerve graft. A further experimental and clinical application of microvascular techniques. Plast Reconstr Surg. 1976;57:413–26.PubMedCrossRefGoogle Scholar
  316. 316.
    Teng FY, Tang BL. Why do Nogo/Nogo-66 receptor gene knockouts result in inferior regeneration compared to treatment with neutralizing agents? J Neurochem. 2005;94:865–74.PubMedCrossRefGoogle Scholar
  317. 317.
    Tennant KA. Thinking outside the brain: structural plasticity in the spinal cord promotes recovery from cortical stroke. Exp Neurol. 2014;254:195–9.PubMedCrossRefGoogle Scholar
  318. 318.
    Tong J, Liu W, Wang X, Han X, Hyrien O, Samadani U, Smith DH, Huang JH. Inhibition of Nogo-66 receptor 1 enhances recovery of cognitive function after traumatic brain injury in mice. J Neurotrauma. 2013;30:247–58.PubMedPubMedCentralCrossRefGoogle Scholar
  319. 319.
    Tong J, Ren Y, Wang X, Dimopoulos VG, Kesler HN, Liu W, He X, Nedergaard M, Huang JH. Assessment of Nogo-66 receptor 1 function in vivo after spinal cord injury. Neurosurgery. 2014;75:51–60.PubMedPubMedCentralCrossRefGoogle Scholar
  320. 320.
    Tsai EC, Krassioukov AV, Tator CH. Corticospinal regeneration into lumbar grey matter correlates with locomotor recovery after complete spinal cord transection and repair with peripheral nerve grafts, fibroblast growth factor 1, fibrin glue, and spinal fusion. J Neuropathol Exp Neurol. 2005;64:230–44.PubMedCrossRefGoogle Scholar
  321. 321.
    van de Meent H, Schwab ME. Regeneration of the lesioned spinal cord. Neurorehabilitation. 1998;10:119–29.PubMedCrossRefGoogle Scholar
  322. 322.
    Vanek P, Thallmair M, Schwab ME, Kapfhammer JP. Increased lesion-induced sprouting of corticospinal fibres in the myelin-free rat spinal cord. Eur J Neurosci. 1998;10:45–56.PubMedCrossRefGoogle Scholar
  323. 323.
    Varga ZM, Schwab ME, Nicholls JG. Myelin-associated neurite growth-inhibitory proteins and suppression of regeneration of immature mammalian spinal cord in culture. Proc Natl Acad Sci U S A. 1995;92:10959–63.PubMedPubMedCentralCrossRefGoogle Scholar
  324. 324.
    Vasudeva VS, Abd-El-Barr M, Chi J. Lumbosacral spinal cord epidural stimulation enables recovery of voluntary movement after complete motor spinal cord injury. Neurosurgery. 2014;75:N14–5.PubMedCrossRefGoogle Scholar
  325. 325.
    Volpe BT, Krebs HI, Hogan N, Edelstein L, Diels C, Aisen M. A novel approach to stroke rehabilitation. Neurology. 2000;54:1938–44.PubMedCrossRefGoogle Scholar
  326. 326.
    von Meyenburg J, Brosamle C, Metz GA, Schwab ME. Regeneration and sprouting of chronically injured corticospinal tract fibers in adult rats promoted by NT-3 and the mAb IN-1, which neutralizes myelin-associated neurite growth inhibitors. Exp Neurol. 1998;154:583–94.CrossRefGoogle Scholar
  327. 327.
    Walchli T, Pernet V, Weinmann O, Shiu JY, Guzik-Kornacka A, Decrey G, Yuksel D, Schneider H, Vogel J, Ingber DE, Vogel V, Frei K, Schwab ME. Nogo-A is a negative regulator of CNS angiogenesis. Proc Natl Acad Sci U S A. 2013;110:E1943–52.PubMedPubMedCentralCrossRefGoogle Scholar
  328. 328.
    Wall A, Borg J, Palmcrantz S. Clinical application of the Hybrid Assistive Limb (HAL) for gait training-a systematic review. Front Syst Neurosci. 2015;9:48.PubMedPubMedCentralCrossRefGoogle Scholar
  329. 329.
    Wang X, Messing A, David S. Axonal and nonneuronal cell responses to spinal cord injury in mice lacking glial fibrillary acidic protein. Exp Neurol. 1997;148:568–76.PubMedCrossRefGoogle Scholar
  330. 330.
    Wang KC, Kim JA, Sivasankaran R, Segal R, He Z. P75 interacts with the Nogo receptor as a co-receptor for Nogo, MAG and OMgp. Nature. 2002;420:74–8.PubMedCrossRefGoogle Scholar
  331. 331.
    Wang X, Duffy P, McGee AW, Hasan O, Gould G, Tu N, Harel NY, Huang Y, Carson RE, Weinzimmer D, Ropchan J, Benowitz LI, Cafferty WB, Strittmatter SM. Recovery from chronic spinal cord contusion after Nogo receptor intervention. Ann Neurol. 2011;70:805–21.PubMedPubMedCentralCrossRefGoogle Scholar
  332. 332.
    Wang D, Ichiyama RM, Zhao R, Andrews MR, Fawcett JW. Chondroitinase combined with rehabilitation promotes recovery of forelimb function in rats with chronic spinal cord injury. J Neurosci. 2011;31:9332–44.PubMedCrossRefGoogle Scholar
  333. 333.
    Wanner M, Lang DM, Bandtlow CE, Schwab ME, Bastmeyer M, Stuermer CA. Reevaluation of the growth-permissive substrate properties of goldfish optic nerve myelin and myelin proteins. J Neurosci. 1995;15:7500–8.PubMedGoogle Scholar
  334. 334.
    Warren PM, Alilain WJ. The challenges of respiratory motor system recovery following cervical spinal cord injury. Prog Brain Res. 2014;212:173–220.PubMedCrossRefGoogle Scholar
  335. 335.
    Weibel D, Cadelli D, Schwab ME. Regeneration of lesioned rat optic nerve fibers is improved after neutralization of myelin-associated neurite growth inhibitors. Brain Res. 1994;642:259–66.PubMedCrossRefGoogle Scholar
  336. 336.
    Weinmann O, Schnell L, Ghosh A, Montani L, Wiessner C, Wannier T, Rouiller E, Mir A, Schwab ME. Intrathecally infused antibodies against Nogo-A penetrate the CNS and downregulate the endogenous neurite growth inhibitor Nogo-A. Mol Cell Neurosci. 2006;32:161–73.PubMedCrossRefGoogle Scholar
  337. 337.
    Wenger N, Moraud EM, Raspopovic S, Bonizzato M, DiGiovanna J, Musienko P, Morari M, Micera S, Courtine G. Closed-loop neuromodulation of spinal sensorimotor circuits controls refined locomotion after complete spinal cord injury. Sci Transl Med. 2014;6:255ra133.PubMedCrossRefGoogle Scholar
  338. 338.
    Wettels N, Fishel JA, Loeb GE. Multimodal tactile sensor. In: Balasubramanian R, Santos VJ, editors. The human hand as an inspiration for robot hand development, Springer Tracts in Advanced Robotics (STAR) series. Springer: Heidelberg; 2014.Google Scholar
  339. 339.
    Willand MP, Holmes M, Bain JR, de Bruin H, Fahnestock M. Sensory nerve cross-anastomosis and electrical muscle stimulation synergistically enhance functional recovery of chronically denervated muscle. Plast Reconstr Surg. 2014;134:736e–45.PubMedCrossRefGoogle Scholar
  340. 340.
    Willi R, Aloy EM, Yee BK, Feldon J, Schwab ME. Behavioral characterization of mice lacking the neurite outgrowth inhibitor Nogo-A. Genes Brain Behav. 2009;8:181–92.PubMedCrossRefGoogle Scholar
  341. 341.
    Williams LR, Longo FM, Powell HC, Lundborg G, Varon S. Spatial-temporal progress of peripheral nerve regeneration within a silicone chamber: parameters for a bioassay. J Comp Neurol. 1983;218:460–70.PubMedCrossRefGoogle Scholar
  342. 342.
    Williams G, Wood A, Williams EJ, Gao Y, Mercado ML, Katz A, Joseph-McCarthy D, Bates B, Ling HP, Aulabaugh A, Zaccardi J, Xie Y, Pangalos MN, Walsh FS, Doherty P. Ganglioside inhibition of neurite outgrowth requires Nogo receptor function: identification of interaction sites and development of novel antagonists. J Biol Chem. 2008;283:16641–52.PubMedCrossRefGoogle Scholar
  343. 343.
    Windle WF. Recollections of research in spinal cord regeneration. Exp Neurol. 1981;71:1–5.PubMedCrossRefGoogle Scholar
  344. 344.
    Wirz M, Dietz V. European Multicenter Study of Spinal Cord Injury, N. Recovery of sensorimotor function and activities of daily living after cervical spinal cord injury: the influence of age. J Neurotrauma. 2015;32:194–9.PubMedCrossRefGoogle Scholar
  345. 345.
    Wolburg H, Kästner R. Is the architecture of astrocytic membrane crucial for axonal regeneration in the central nervous system? Naturwissenschaften. 1984;71:484–5.PubMedCrossRefGoogle Scholar
  346. 346.
    Woolf CJ, Shortland P, Reynolds M, Ridings J, Doubell T, Coggeshall RE. Reorganization of central terminals of myelinated primary afferents in the rat dorsal horn following peripheral axotomy. J Comp Neurol. 1995;360:121–34.PubMedCrossRefGoogle Scholar
  347. 347.
    Worter V, Schweigreiter R, Kinzel B, Mueller M, Barske C, Bock G, Frentzel S, Bandtlow CE. Inhibitory activity of myelin-associated glycoprotein on sensory neurons is largely independent of NgR1 and NgR2 and resides within Ig-Like domains 4 and 5. e5218. 2009;4.Google Scholar
  348. 348.
    Wu P, Spinner RJ, Gu Y, Yaszemski MJ, Windebank AJ, Wang H. Delayed repair of the peripheral nerve: a novel model in the rat sciatic nerve. J Neurosci Methods. 2013;214:37–44.PubMedCrossRefGoogle Scholar
  349. 349.
    Wu P, Chawla A, Spinner RJ, Yu C, Yaszemski MJ, Windebank AJ, Wang H. Key changes in denervated muscles and their impact on regeneration and reinnervation. Neural Regen Res. 2014;9:1796–809.PubMedPubMedCentralCrossRefGoogle Scholar
  350. 350.
    Xu C, Kou Y, Zhang P, Han N, Yin X, Deng J, Chen B, Jiang B. Electrical stimulation promotes regeneration of defective peripheral nerves after delayed repair intervals lasting under one month. PLoS One. 2014;9:e105045.PubMedPubMedCentralCrossRefGoogle Scholar
  351. 351.
    Xu B, Park D, Ohtake Y, Li H, Hayat U, Liu J, Selzer ME, Longo FM, Li S. Role of CSPG receptor LAR phosphatase in restricting axon regeneration after CNS injury. Neurobiol Dis. 2015;73:36–48.PubMedCrossRefGoogle Scholar
  352. 352.
    Yang YS, Harel NY, Strittmatter SM. Reticulon-4A (Nogo-A) redistributes protein disulfide isomerase to protect mice from SOD1-dependent amyotrophic lateral sclerosis. J Neurosci. 2009;29:13850–9.PubMedPubMedCentralCrossRefGoogle Scholar
  353. 353.
    Yang ML, Li JJ, So KF, Chen JY, Cheng WS, Wu J, Wang ZM, Gao F, Young W. Efficacy and safety of lithium carbonate treatment of chronic spinal cord injuries: a double-blind, randomized, placebo-controlled clinical trial. Spinal Cord. 2012;50:141–6.PubMedCrossRefGoogle Scholar
  354. 354.
    Yick LW, So KF, Cheung PT, Wu WT. Lithium chloride reinforces the regeneration-promoting effect of chondroitinase ABC on rubrospinal neurons after spinal cord injury. J Neurotrauma. 2004;21:932–43.PubMedCrossRefGoogle Scholar
  355. 355.
    Young W. Review of lithium effects on brain and blood. Cell Transplant. 2009;18:951–75.PubMedCrossRefGoogle Scholar
  356. 356.
    Young W. Spinal cord regeneration. Cell Transplant. 2014;23:573–611.PubMedCrossRefGoogle Scholar
  357. 357.
    Young W. Electrical stimulation and motor recovery. Cell Transplant. 2015;24:429–46.PubMedCrossRefGoogle Scholar
  358. 358.
    Yu J, Fernandez-Hernando C, Suarez Y, Schleicher M, Hao Z, Wright PL, DiLorenzo A, Kyriakides TR, Sessa WC. Reticulon 4B (Nogo-B) is necessary for macrophage infiltration and tissue repair. Proc Natl Acad Sci U S A. 2009;106:17511–6.PubMedPubMedCentralCrossRefGoogle Scholar
  359. 359.
    Yu Z, Yu P, Chen H, Geller HM. Targeted inhibition of KCa3.1 attenuates TGF-beta-induced reactive astrogliosis through the Smad2/3 signaling pathway. J Neurochem. 2014;130:41–9.PubMedPubMedCentralCrossRefGoogle Scholar
  360. 360.
    Yuan J, Zou M, Xiang X, Zhu H, Chu W, Liu W, Chen F, Lin J. Curcumin improves neural function after spinal cord injury by the joint inhibition of the intracellular and extracellular components of glial scar. J Surg Res. 2015;195:235–45.PubMedCrossRefGoogle Scholar
  361. 361.
    Zagrebelsky M, Buffo A, Skerra A, Schwab ME, Strata P, Rossi F. Retrograde regulation of growth-associated gene expression in adult rat Purkinje cells by myelin-associated neurite growth inhibitory proteins. J Neurosci. 1998;18:7912–29.PubMedGoogle Scholar
  362. 362.
    Zagrebelsky M, Schweigreiter R, Bandtlow CE, Schwab ME, Korte M. Nogo-A stabilizes the architecture of hippocampal neurons. J Neurosci. 2010;30:13220–34.PubMedCrossRefGoogle Scholar
  363. 363.
    Zemmar A, Weinmann O, Kellner Y, Yu X, Vicente R, Gullo M, Kasper H, Lussi K, Ristic Z, Luft AR, Rioult-Pedotti M, Zuo Y, Zagrebelsky M, Schwab ME. Neutralization of Nogo-A enhances synaptic plasticity in the rodent motor cortex and improves motor learning in vivo. J Neurosci. 2014;34:8685–98.PubMedPubMedCentralCrossRefGoogle Scholar
  364. 364.
    Zhang D, Utsumi T, Huang HC, Gao L, Sangwung P, Chung C, Shibao K, Okamoto K, Yamaguchi K, Groszmann RJ, Jozsef L, Hao Z, Sessa WC, Iwakiri Y. Reticulon 4B (Nogo-B) is a novel regulator of hepatic fibrosis. Hepatology. 2011;53:1306–15.PubMedPubMedCentralCrossRefGoogle Scholar
  365. 365.
    Zhang L, Kaneko S, Kikuchi K, Sano A, Maeda M, Kishino A, Shibata S, Mukaino M, Toyama Y, Liu M, Kimura T, Okano H, Nakamura M. Rewiring of regenerated axons by combining treadmill training with semaphorin3A inhibition. Mol Brain. 2014;7:14.PubMedPubMedCentralCrossRefGoogle Scholar
  366. 366.
    Zhao RR, Muir EM, Alves JN, Rickman H, Allan AY, Kwok JC, Roet KC, Verhaagen J, Schneider BL, Bensadoun JC, Ahmed SG, Yanez-Munoz RJ, Keynes RJ, Fawcett JW, Rogers JH. Lentiviral vectors express chondroitinase ABC in cortical projections and promote sprouting of injured corticospinal axons. J Neurosci Methods. 2011;201:228–38.PubMedPubMedCentralCrossRefGoogle Scholar
  367. 367.
    Zhao RR, Fawcett JW. Combination treatment with chondroitinase ABC in spinal cord injury – breaking the barrier. Neurosci Bull. 2013;29:477–83.PubMedPubMedCentralCrossRefGoogle Scholar
  368. 368.
    Zhou HX, Li XY, Li FY, Liu C, Liang ZP, Liu S, Zhang B, Wang TY, Chu TC, Lu L, Ning GZ, Kong XH, Feng SQ. Targeting RPTPsigma with lentiviral shRNA promotes neurites outgrowth of cortical neurons and improves functional recovery in a rat spinal cord contusion model. Brain Res. 2014;1586:46–63.PubMedCrossRefGoogle Scholar
  369. 369.
    Zhu H, Feng YP, Young W, You SW, Shen XF, Liu YS, Ju G. Early neurosurgical intervention of spinal cord contusion: an analysis of 30 cases. Chin Med J (Engl). 2008;121:2473–8.Google Scholar
  370. 370.
    Zhu Z, Kremer P, Tadmori I, Ren Y, Sun D, He X, Young W. Lithium suppresses astrogliogenesis by neural stem and progenitor cells by inhibiting STAT3 pathway independently of glycogen synthase kinase 3 beta. PLoS One. 2011;6:e23341.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2017

Authors and Affiliations

  1. 1.Rutgers, The State University of New JerseyNew BrunswickUSA

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