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Models of CNS injury in the nonhuman primate: A new era for treatment strategies

  • Review Article
  • Published:
Translational Neuroscience

Abstract

Central nervous system (CNS) injuries affect all levels of society indiscriminately, resulting in functional and behavioral deficits with devastating impacts on life expectancies, physical and emotional wellbeing. Considerable literature exists describing the pathophysiology of CNS injuries as well as the cellular and molecular factors that inhibit regrowth and regeneration of damaged connections. Based on these data, numerous therapeutic strategies targeting the various factors of repair inhibition have been proposed and on-going assessment has demonstrated some promising results in the laboratory environ. However, several of these treatment strategies have subsequently been taken into clinical trials but demonstrated little to no improvement in patient outcomes. As a result, options for clinical interventions following CNS injuries remain limited and effective restorative treatment strategies do not as yet exist. This review discusses some of the current animal models, with focus on nonhuman primates, which are currently being modeled in the laboratory for the study of CNS injuries. Last, we review the current understanding of the mechanisms underlying repair/regrowth inhibition and the current trends in experimental treatment strategies that are being assessed for potential translation to clinical applications.

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References

  1. Morganti-Kossmann M. C., Yan E., Bye N., Animal models of traumatic brain injury: is there an optimal model to reproduce human brain injury in the laboratory? Injury, 2010, 41,Suppl. 1, S10–S13

    Article  PubMed  Google Scholar 

  2. Eltzschig H. K., Eckle T., Ischemia and reperfusion — from mechanism to translation, Nat. Med., 2011, 17, 1391–1401

    Article  PubMed  CAS  Google Scholar 

  3. Onifer S. M., Smith G. M., Fouad K., Plasticity after spinal cord injury: relevance to recovery and approaches to facilitate it, Neurotherapeutics, 2011, 8, 283–293

    Article  PubMed  Google Scholar 

  4. Lai M. C., Yang S. N., Perinatal hypoxic-ischemic encephalopathy, J. Biomed. Biotechnol., 2011, 609813

  5. Coronado V. G., Xu L., Basavaraju S. V., McGuire L. C., Wald M. M., Faul M. D., Guzman B. R., et al., Surveillance for traumatic brain injuryrelated deaths - United States, 1997–2007, MMWR Surveill. Summ., 2011, 60, 1–32

    PubMed  Google Scholar 

  6. Foundation for spinal cord injury prevention, C. A. C., Spinal cord injury facts [online]. Available: http://www.fscip.org/facts.htm [accessed 2 March 2012]

  7. Smith J., Wells L., Dodd K., The continuing fall in incidence of hypoxicischemic encephalopathy in term infants, BJOG, 2000, 107, 461–466

    Article  PubMed  CAS  Google Scholar 

  8. Williams G. R., Jiang J. G., Matchar D. B., Samsa G. P., Incidence and occurrence of total (first-ever and recurrent) stroke, Stroke, 1999, 30, 2523–2528

    Article  PubMed  CAS  Google Scholar 

  9. Narayan R. K., Michel M. E., Ansell B., Baethmann A., Biegon A., Bracken M. B., et al., Clinical trials in head injury, J. Neurotrauma, 2002, 19, 503–557

    Article  PubMed  Google Scholar 

  10. Millen J. E., Glauser F. L., Fairman R. P., A comparison of physiological responses to percussive brain trauma in dogs and sheep, J. Neurosurg., 1985, 62, 587–591

    Article  PubMed  CAS  Google Scholar 

  11. Pfenninger E. G., Reith A., Breitig D., Grunert A., Ahnefeld F. W., Early changes of intracranial pressure, perfusion pressure, and blood flow after acute head injury. Part 1: An experimental study of the underlying pathophysiology, J. Neurosurg., 1989, 70, 774–779

    Article  PubMed  CAS  Google Scholar 

  12. Vink R., Bahtia K. D., Reilly P. L., The relationship between intracranial pressure and brain oxygenation following brain injury in sheep, Acta Neurochir. Suppl., 102, 189–192

  13. Boyce V. S., Tumulo M., Fischer I., Murray M, Lemay M. A., Neurotrophic factors promote and enhance locomotor recovery in untrained spinalized cats, J. Neurophysiol., 2007, 98, 1988–1996

    Article  PubMed  Google Scholar 

  14. Jefferson S. C., Tester N. J., Howland D. R., Chondroitinase ABC promotes recovery of adaptive limb movements and enhances axonal growth caudal to a spinal hemisection, J. Neurosci., 2011, 5710–5720

  15. Kishimoto N., Shimizu K., Sawamoto K., Neuronal regeneration in a zebrafish model of adult brain injury, Dis. Model. Mech., 2012, 5, 200–209

    Article  PubMed  CAS  Google Scholar 

  16. Inder T., Neil J., Yoder B., Rees S., Non-human primate models of neonatal brain injury, Semin. Perinatol., 2004, 28, 396–404

    Article  PubMed  Google Scholar 

  17. De Crespigny A., J., D’Arceuil H. E., Maynard K. I., He J., McAuliffe D., Norbach A., Sehgal P. K., et al., Acute studies of a new primate model of reversible middle cerebral artery occlusion, J. Stroke Cerebrovasc. Dis., 2005, 14, 80–87

    Article  PubMed  Google Scholar 

  18. Fukuda S, Del Zoppo G., Models of focal cerebral ischemia in the nonhuman primate, ILAR J., 2003, 44, 96–104

    PubMed  CAS  Google Scholar 

  19. Felleman D. J., Van Essen D. C., Distributed hierarchical processing in the primate cerebral cortex, Cereb. Cortex, 1991, 1, 1–47

    Article  PubMed  CAS  Google Scholar 

  20. Rosa M. G., Visual maps in the adult primate cerebral cortex: some implications for brain development and evolution, Braz. J. Med. Biol. Res., 2002, 35, 1485–1498

    Article  PubMed  CAS  Google Scholar 

  21. Schmid M. C., Mrowka S. W., Turchi J., Saunders R. C., Wilke M., Peters A. J., et al., Blindsight depends on the lateral geniculate nucleus, Nature, 2010, 466, 373–377

    Article  PubMed  CAS  Google Scholar 

  22. Fonta C., Imbert M., Vascularization in the primate visual cortex during development, Cereb. Cortex, 2002, 12, 199–211

    Article  PubMed  Google Scholar 

  23. Virley D., Hadingham S. J., Roberts J. C., Farnfield B., Elliott H., Whelan G., et al., A new primate model of focal stroke: endothelin-1-induced middle cerebral artery occlusion and reperfusion in the common marmoset, J. Cereb. Blood Flow Metab., 2004, 24, 24–41

    Article  PubMed  CAS  Google Scholar 

  24. Schwartz A. E., Pile-Spellman J., New model of reperfused stroke by occlusion of the anterior cerebral artery in baboons, Acta Neurochir. (Wien), 2011, 153, 327–331

    Article  Google Scholar 

  25. Garcia J. H., Kamijyo Y., Cerebral infarction. Evolution of histopathological changes after occlusion of a middle cerebral artery in primates, J. Neuropathol. Exp. Neurol., 1974, 33, 408–421

    Article  PubMed  CAS  Google Scholar 

  26. Crowell R. M., Marcoux F. W., DeGirolami U., Variability and reversibility of focal cerebral ischemia in unanesthetized monkeys, Neurology, 1981, 31, 1295–1302

    Article  PubMed  CAS  Google Scholar 

  27. Spetzler R. F., Selman W. R., Weinstein P., Townsend J., Mehdorn M., Telles D., et al., Chronic reversible cerebral ischemia: evaluation of a new baboon model, Neurosurgery, 1980, 7, 257–261

    Article  PubMed  CAS  Google Scholar 

  28. Kito G., Nishimura A., Susumu T., Nagata R., Kuge Y., Yokota C., et al., Experimental thromboembolic stroke in cynomolgus monkey, J. Neurosci. Methods, 2001, 105, 45–53

    Article  PubMed  CAS  Google Scholar 

  29. Dunn I. F., Kim A. H., Gormley W. B., Brain trauma, In: Encyclopedia of neuroscience (ed. Larry R. S.), Oxford: Academic Press, 2009

    Google Scholar 

  30. Meythaler J. M., Peduzzi J. D., Eleftheriou E., Novack T. A., Current concepts: Diffuse axonal injury associated traumatic brain injury, Arch. Phys. Med. Rehab., 2001, 82, 1461–1471

    Article  CAS  Google Scholar 

  31. Cernak I., Animal models of head trauma, NeuroRx, 2005, 2, 410–422

    Article  PubMed  Google Scholar 

  32. Weber J. T., Experimental models of repetitive brain injuries, Prog. Brain Res., 2007, 161, 253–261

    Article  PubMed  Google Scholar 

  33. Goldshmit Y., Bourne J., Upregulation of EphA4 on astrocytes potentially mediates astrocytic gliosis after cortical lesion in the marmoset monkey, J. Neurotrauma, 2010, 27, 1321–1332

    Article  PubMed  Google Scholar 

  34. Rosenfeld J. V., A neurosurgeon in Iraq: a personal perspective, J. Clin. Neurosci., 2006, 13, 986–990

    Article  PubMed  Google Scholar 

  35. Foroughi M., Kemeny A. A., Lehecka M., Wons J., Kajdi L., Hatfield R., et al., Operative intervention for delayed symptomatic radionecrotic masses developing following stereotactic radiosurgery for cerebral arteriovenous malformations — case analysis and literature review, Acta Neurochir. (Wien), 2010, 152, 803–815

    Article  Google Scholar 

  36. Moseley B. D., Nickels K., Wirrell E. C., Surgical outcomes for intractable epilepsy in children with epileptic spasms, J. Child Neurol., 2011, [Epub ahead of print]

  37. Kazama A., Bechevalier J., Selective aspiration or neurotoxic lesions of orbital frontal areas 11 and 13 spared monkeys’ performance on the object discrimination reversal task, J. Neurosci., 2009, 29, 2794–2804

    Article  PubMed  CAS  Google Scholar 

  38. Rudebeck P. H., Murray E. A., Amygdala and orbitofrontal cortex lesions differentially influence choices during object reversal learning, J. Neurosci., 2008, 28, 8338–8343

    Article  PubMed  CAS  Google Scholar 

  39. Rudebeck P. H., Murray E. A., Dissociable effects of subtotal lesions within the macaque orbital prefrontal cortex on reward-guided behavior, J. Neurosci., 2011, 31, 10569–10578

    Article  PubMed  CAS  Google Scholar 

  40. Gennarelli T. A., Thibault L. E., Adams J. H., Graham D. I., Thompson C. J., Marcincin R. P., Diffuse axonal injury and traumatic coma in the primate, Ann. Neurol., 1982, 12, 564–574

    Article  PubMed  CAS  Google Scholar 

  41. Hofman M. A., Size and shape of the cerebral cortex in mammals. I. The cortical surface, Brain Behav. Evol., 1985, 27, 28–40

    Article  PubMed  CAS  Google Scholar 

  42. Hofman M. A., Size and shape of the cerebral cortex in mammals. II. The cortical volume, Brain Behav. Evol., 1988, 32, 17–26

    Article  PubMed  CAS  Google Scholar 

  43. Zhang K., Sejnowski T. J., A universal scaling law between gray matter and white matter of cerebral cortex, Proc. Natl. Acad. Sci. USA, 2000, 97, 5621–5626

    Article  PubMed  CAS  Google Scholar 

  44. Herculano-Houzel S., Mota B., Wong P., Kaas J. H., Connectivity-driven white matter scaling and folding in primate cerebral cortex, Proc. Natl. Acad. Sci. USA, 2010, 107, 19008–19013

    Article  PubMed  CAS  Google Scholar 

  45. Kadhim H., Sebire G., Kahn A., Evrad P., Dan B., Causal mechanisms underlying periventricular leukomalacia and cerebral palsy, Curr. Ped. Rev., 2005, 1, 1–6

    Article  CAS  Google Scholar 

  46. Bergman I, Bauer R. E., Barmada M. A., Latchaw R. E., Taylor H. G., David R., et al., Intracerebral hemorrhage in the full-term neonatal infant, Pediatrics, 1985, 75, 488–496

    PubMed  CAS  Google Scholar 

  47. Zhang Y. W., Chen Y. H., [Effects of hypoxia-ischemia on differential neural cells in subventricular zone of human fetus], Zhonghua Er. Ke. Za. Zhi., 2008, 46, 644–647

    PubMed  Google Scholar 

  48. Morales P., Fiedler J. L., Andres S., Berrios C., Huaiquin P., Bustamante D., et al., Plasticity of hippocampus following perinatal asphyxia: effects on postnatal apoptosis and neurogenesis, J. Neurosci. Res., 2008, 86, 2650–2662

    Article  PubMed  CAS  Google Scholar 

  49. Perlman J. M., Summary proceedings from the neurology group on hypoxic-ischemic encephalopathy, Pediatrics, 2006, 117, S28–S33

    Article  PubMed  Google Scholar 

  50. Sloper J. J., Johnson P., Powell T. P. S., Selective degeneration of interneurons in the motor cortex of infant monkeys following controlled hypoxia: a possible cause of epilepsy, Brain Res., 1980, 198, 204–209

    Article  PubMed  CAS  Google Scholar 

  51. Myers R. E., Atrophic cortical sclerosis associated with status marmoratus in a perinatally damaged monkey, Neurology, 1969, 19, 1177–1188

    Article  PubMed  CAS  Google Scholar 

  52. Myers R. E., Two patterns of perinatal brain damage and their conditions of occurrence, Am. J. Obstet. Gynecol., 1972, 112, 246–276

    PubMed  CAS  Google Scholar 

  53. Myers R. E., A unitary theory of causation of anoxic and hypoxic brain pathology, Adv. Neurol., 1979, 26, 195–213

    PubMed  CAS  Google Scholar 

  54. Adamsons K., Mueller-Heubach E., Myers R.E., Production of fetal asphyxia in the rhesus monkey by administration of catecholamines to the mother, Am. J. Obstet. Gynecol., 1971, 109, 248–262

    PubMed  CAS  Google Scholar 

  55. Brann A. W. Jr., Myers R. E., Cental nervous system findings in the newborn monkey following severe in utero partial asphyxia, Neurology, 1975, 25, 327–338

    Article  PubMed  Google Scholar 

  56. Inder T., Neil J., Yoder B., Rees S., Non-human primate models of neonatal brain injury. Semin. Perinatol., 2004, 28, 396–404

    Article  PubMed  Google Scholar 

  57. Hagberg H., Ichord R., Palmer C., Yager J. Y., Vannucci S. J., Animal models of developmental brain injury: relevance to human disease. A summary of the panel discussion from the Third Hershey Conference on developmental cerebral blood flow and metabolism, Dev. Neurosci., 2002, 24, 364–366

    Article  PubMed  CAS  Google Scholar 

  58. Yager J. Y., Ashwal S., Animal models of perinatal hypoxic-ischemic brain damage, Pediatr. Neurol., 2009, 40, 156–167

    Article  PubMed  Google Scholar 

  59. Lemons M. L., Howland D. R., Anderson D. K., Chondroitin sulfate proteoglycan immunoreactivity increases following spinal cord injury and transplantation, Exp. Neurol., 1999, 160, 51–65

    Article  PubMed  CAS  Google Scholar 

  60. Merkler D., Metz G. A., Raineteau O., Dietz V., Schwab M. E., Fouad K., Locomotor recovery in spinal cord-injured rats treated with an antibody neutralizing the myelin-associated neurite growth inhibitor Nogo-A., J. Neurosci., 2001, 21, 3665–3673

    PubMed  CAS  Google Scholar 

  61. Raineteau O., Fouad K., Bareyre F. M., Schwab M. E., Reorganization of descending motor tracts in the rat spinal cord, Eur. J. Neurosci., 2002, 16, 1761–1771

    Article  PubMed  Google Scholar 

  62. Gonzenbach R. R., Gasser P., Zorner B., Hochreutener R., Dietz V., Schwab M. E., Nogo-A antibodies and training reduce muscle spasms in spinal cord-injured rats, Ann. Neurol., 2010, 68, 48–57

    Article  PubMed  Google Scholar 

  63. Darian-Smith C., Brown S., Functional changes at periphery and cortex following dorsal root lesions in adult monkeys, Nat. Neurosci., 2000, 3, 476–481

    Article  PubMed  CAS  Google Scholar 

  64. Babu R. S., Muthusamy R., Namasivayam A., Behavioural assessment of functional recovery after spinal cord hemisection in the bonnet monkey (Macaca radiate), J. Neurol. Sci., 2000, 178, 136–152

    Article  Google Scholar 

  65. Babu R. S., Namasivayam A, Sridevi D., Periasamy P., Sunandhini R. L., Locomotor behavior of bonnet monkeys after spinal contusion injury: footprint study, Synapse, 2012, 66, 509–521

    Article  CAS  Google Scholar 

  66. Babu R. S., Anand P., Jeraud M., Periasamy P., Namasivayam A., Bipedal locomotion of bonnet macaques after spinal cord injury, Motor Control, 2007, 11, 322–347

    PubMed  Google Scholar 

  67. Babu R. S., Periasamy P., Varadamurthy S., Sethuraman O. S., Namasivayam A, Locomotor behavior of bonnet macaques after spinal cord injury, Motor Control, 2007, 11, 71–85

    PubMed  Google Scholar 

  68. Babu R. S., Namasivayam A., Recovery of bipedal locomotion in bonnet macaques after spinal cord injury: footprint analysis, Synapse, 2008, 62, 432–447

    Article  PubMed  CAS  Google Scholar 

  69. Nout Y. S., Ferguson A. R., Strand S. C., Moseanko R., Hawbecker S., Zdunowski S., et al., Methods for functional assessment after C7 spinal cord hemisection in the rhesus monkey, Neurorehabil. Neural Repair, 2012, [Epub ahead of print]

  70. Valent L., Dallmeijer A., Houdijk H., Talsma E., Van der Woude L., The effects of upper body exercise on the physical capacity of people with a spinal cord injury: a systematic review, Clin. Rehabil., 2007, 21, 315–330

    Article  PubMed  Google Scholar 

  71. Valent L. J., Dallmeijer A. J., Houdijk H., Slootman H. J., Janssen T. W., Post M. W., et al., Effects of hand cycle training on physical capacity in individuals with tetraplegia: a clinical trial, Phys. Ther., 2009, 89, 1051–1060

    Article  PubMed  Google Scholar 

  72. Spooren A. I., Janssen-Potten Y. J., Kerckhofs E., Seelen H. A., Outcome of motor training programmes on arm and hand functioning in patients with cervical spinal cord injury according to different levels of the ICF: a systematic review, J. Rehabil. Med., 2009, 41, 497–505

    Article  PubMed  Google Scholar 

  73. Harvey L. A., Dunlop S. A., Churilov L., Hsueh Y. S., Galea M. P., Early intensive hand rehabilitation after spinal cord injury (“Hands on”): a protocol for a randomized controlled trial, Trials, 2011, 12, 14

    Article  PubMed  Google Scholar 

  74. Magnuson D. S., Smith R. R., Brown E. H., Enzmann G., Angeli C., Quesada P. M., et al., Swimming as a model of task-specific locomotor retraining after spinal cord injury in the rat, Neurorehabil. Neural Repair, 2009, 23, 535–545

    Article  PubMed  Google Scholar 

  75. Smith R. R., Brown E. H., Shum-Siu A., Whelan A., Burke D. A., Benton R. L., et al., Swim training initiated acutely after spinal cord injury is ineffective and induces extravasation in and around the epicenter, J. Neurotrauma, 2009, 26, 1017–1027

    Article  PubMed  Google Scholar 

  76. Onifer S. M., Zhang O., Whitnel-Smith L. K., Raza K., O’Dell C. R., Lyttle T., et al., Horizontal ladder task-specific re-training in adult rats with contusive thoracic spinal cord injury, Restor. Neurol. Neurosci., 2011, 29, 275–286

    PubMed  Google Scholar 

  77. Nout Y. S., Rosenzweig E. S., Brock J. H., Strand S. C., Moseanko R., Hawbecker S., et al., Animal models of neurologic disorders: a nonhuman primate model of spinal cord injury, Neurotherapeutics, 2012, 9, 380–392

    Article  PubMed  CAS  Google Scholar 

  78. Courtine G., Bunge M. B., Fawcett J. W., Grossman R. G., Kaas J. H., Lemon R., et al., Can experiments in nonhuman primates expedite the translation of treatments for spinal cord injury in humans?, Nat. Med., 2007, 13, 561–566

    Article  PubMed  CAS  Google Scholar 

  79. Lemon R. N., Griffiths J., Comparing the function of the corticospinal system in different species: organizational differences for motor specialization? Muscle Nerve, 2005, 32, 261–279

    Article  PubMed  Google Scholar 

  80. Del Zoppo G. J., Sharp F. R., Heiss W. D., Albers G. W., Heterogeneity in the penumbra, J. Cerebr. Blood Flow Metab., 2011, 31, 1836–1851

    Article  Google Scholar 

  81. Broughton B. R., Reutens D. C., Sobey C. G., Apoptotic mechanisms after cerebral ischemia, Stroke, 2009, 40, e331–339

    Article  PubMed  Google Scholar 

  82. Kerr J. F., Wyllie A. H., Currie A. R., Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics, Br. J. Cancer, 1972, 26, 239–257

    Article  PubMed  CAS  Google Scholar 

  83. Yang Y., Rosenberg G. A., Blood-brain barrier breakdown in acute and chronic cerebrovascular disease, Stroke, 2011, 42, 3323–3328

    Article  PubMed  CAS  Google Scholar 

  84. Eugenin E. A., Berman J. W., Chemokine-dependent mechanism of leukocyte trafficking across a model of the blood-brain barrier, Methods, 2003, 29, 351–361

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  86. O’Connell K. M., The role of free radicals in traumatic brain injury, Biol. Res. Nurs., 2012, [Epub ahead of print]

  87. Wang J. T., Medress Z. A., Barres B. A., Axon degeneration: molecular mechanisms of a self-destruction pathway, J. Cell Biol., 2012, 196, 7–18

    Article  PubMed  CAS  Google Scholar 

  88. Sun F., Lin C. L., McTigue D., Shan X., Tovar C. A., Bresnahan J. C., et al., 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, 2010, 58, 1304–1319

    PubMed  Google Scholar 

  89. Almad A., Sahinkaya F. R., McTigue D. M., Oligodendrocyte fate after spinal cord injury, Neurotherapeutics, 2011, 8, 262–273

    Article  PubMed  Google Scholar 

  90. Silver J., Miller J. H., Regeneration beyond the glial scar, Nat. Rev. Neurosci., 2004, 5, 146–156

    Article  PubMed  CAS  Google Scholar 

  91. Ramón y Cajal, S., Degeneration and regeneration of the nervous system, London: Oxford University Press, 1928

    Google Scholar 

  92. Waller A., Experiments on the section of the glossopharyngeal and hypoglossal nerves of the frog, and observations of the alterations produced thereby in the structure of their primitive fibres, Phil. Trans. R. Soc. Lond., 1850, 140, 423–429

    Article  Google Scholar 

  93. Vargas M. E., Barres B. A., Why is Wallerian degeneration in the CNS so slow? Annu. Rev. Neurosci., 2007, 30, 153–179

    Article  PubMed  CAS  Google Scholar 

  94. Tom V., Steinmetz M. P., Miller J. H., Doller C. M., Silver J., Studies on the development and behavior of the dystrophic growth cone, the hallmark of regeneration failure, in an in vitro model of the glial scar and after spinal cord injury, J. Neurosci., 2004, 24, 6531–6539

    Article  PubMed  CAS  Google Scholar 

  95. David S., Aguayo A., Axonal elongation into peripheral nervous system “bridges” after central nervous system injury in adult rats, Science, 1981, 214, 931–933

    Article  PubMed  CAS  Google Scholar 

  96. Blizzard C. A., Haas M. A., Vickers J. C., Dickson T. C., Cellular dynamics underlying regeneration of damaged axons differs from initial axon development, Eur. J. Neurosci., 2007, 26, 1100–1108

    Article  PubMed  CAS  Google Scholar 

  97. Blizzard C. A., King A. E., Haas M. A., O’Toole D. A., Vickers J. C., Dickson T. C., Axonal shearing in mature cortical neurons induces attempted regeneration and the reestablishment of neurite polarity, Brain Res., 2009, 1300, 24–36

    Article  PubMed  CAS  Google Scholar 

  98. Fawcett J. W., Overcoming inhibition in the damaged spinal cord, J. Neurotrauma, 2006, 23, 371–383

    Article  PubMed  Google Scholar 

  99. Galtrey C. M., Asher R. A., Nothias F., Fawcett J. W., Promoting plasticity in the spinal cord with chondroitinase improves functional recovery after peripheral nerve repair, Brain, 2007, 130, 926–939

    Article  PubMed  Google Scholar 

  100. Araque A., Carmignoto G., Haydon P. G., Dynamic signaling between astrocytes and neurons, Annu. Rev. Physiol., 2001, 63, 795–813

    Article  PubMed  CAS  Google Scholar 

  101. Fellin T., Communication between neurons and astrocytes: relevance to the modulation of synaptic and network activity, J. Neurochem., 2009, 108, 533–544

    Article  PubMed  CAS  Google Scholar 

  102. Goldshmit Y., Galea M. P., Wise G., Bartlett P. F., Turnley A. M., Axonal regeneration and lack of astrocytic gliosis in EphA4-deficient mice, J. Neurosci., 2004, 24, 10064–10073

    Article  PubMed  CAS  Google Scholar 

  103. Dickson B. J., Rho GTPases in growth cone guidance, Curr. Opin. Neurobiol., 2001, 11, 103–110

    Article  PubMed  CAS  Google Scholar 

  104. Carbonell W. S., Mandell J. W., Transient neuronal but persistent astroglial activation of ERK/MAP kinase after focal brain injury in mice, J. Neurotrauma, 2003, 20, 327–336

    Article  PubMed  Google Scholar 

  105. Fawcett J. W., Asher R. A., The glial scar and central nervous system repair, Brain Res. Bull., 1999, 49, 377–391

    Article  PubMed  CAS  Google Scholar 

  106. Smith-Thomas L. C., Fok-Seang J., Stevens J., Du J. S., Muir E., Faissner A., et al., An inhibitor of neurite outgrowth produced by astrocytes, J. Cell Sci., 1994, 107, 1687–1695

    PubMed  CAS  Google Scholar 

  107. Fawcett J., Molecular control of brain plasticity and repair, Prog. Brain Res., 2009, 175, 501–509

    Article  PubMed  CAS  Google Scholar 

  108. Fryer H. J., Kelly G. M., Molinaro L., Hockfield S., The high molecular weight Cat-301 chondroitin sulfate proteoglycan from brain is related to the large aggregating proteoglycan from cartilage, aggrecan, J. Biol. Chem., 1992, 267, 9874–9883

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  110. Koppe G., Bruckner G., Brauer K., Hartig W., Bigl V., Developmental patterns of proteoglycan-containing extracellular matrix in perineuronal nets and neuropil of the postnatal rat brain, Cell Tissue Res., 1997, 288, 33–41

    Article  PubMed  CAS  Google Scholar 

  111. Matthews R. T., Kelly G. M., Zerillo C. A., Gray G., Tiemeyer M., Hockfield S., Aggrecan glycoforms contribute to the molecular heterogeneity of perineuronal nets, J. Neurosci., 2002, 22, 7536–7547

    PubMed  CAS  Google Scholar 

  112. Giamanco K. A., Morawski M., Matthews R. T., Perineuronal net formation and structure in aggrecan knockout mice, Neuroscience, 2010, 170, 1314–1327

    Article  PubMed  CAS  Google Scholar 

  113. Murakami T., Ohtsuka A., Perisynaptic barrier of proteoglycans in the mature brain and spinal cord, Arch. Histol. Cytol., 2003, 66, 195–207

    Article  PubMed  CAS  Google Scholar 

  114. Bruckner G., Szeoke S., Pavlica S., Grosche J, Kacza J., Axon initial segment ensheated by extracellular matrix in perineuronal nets, Neuroscience, 2006, 138, 365–375

    Article  PubMed  CAS  Google Scholar 

  115. Bruckner G., Grosche J., Schmidt S., Hartig W., Margolis R. U., Delpech B., et al., Postnatal development of perineuronal nets in wild-type mice and in a mutant deficient in tenascin-R, J. Comp. Neurol., 2000, 428, 616–629

    Article  PubMed  CAS  Google Scholar 

  116. Bradbury E. J., Carter L. M., Manipulating the glial scar: chondroitinase ABC as a therapy for spinal cord injury, Brain Res. Bull., 2010, 84, 306–316

    Article  PubMed  CAS  Google Scholar 

  117. Bruckner G., Seeger G., Brauer K., Hartig W, Kacza J., Bigl V., Cortical areas are revealed by distribution patterns of proteoglycan components and parvalbumin in the Mongolian gerbil and rat, Brain Res., 1994, 658, 67–86

    Article  PubMed  CAS  Google Scholar 

  118. Deyoe E. A., Hockfield S., Garren H., Van Essen D. C., Antibody labeling of functional subdivisions in visual cortex: Cat-301 immunoreactivity in striate and extrastriate cortex of the macaque monkey, Vis. Neurosci., 1990, 5, 67–81

    Article  PubMed  CAS  Google Scholar 

  119. Homman-Ludiye J., Manger P. R., Bourne J. A., Immunohistochemical parcellation of the ferret (Mustela putorius) visual cortex reveals substantial homology with the cat (Felis catus), J. Comp. Neurol., 2010, 518, 4439–4462

    Article  PubMed  Google Scholar 

  120. Carull D., Laabs T., Geller H. M., Fawcett J. W., Chondroitin sulfate proteoglycans in neural development and regeneration, Curr. Opin. Neurobiol., 2005, 15, 116–120

    Article  CAS  Google Scholar 

  121. Monnier P. P., Sierra A., Schwab J. M., Henke-Fahle S., Mueller B. K., The Rho/ROCK pathway mediates neurite growth-inhibitory activity associated with the chondroitin sulfate proteoglycans of the CNS glial scar, Mol. Cell. Neurosci., 2003, 22, 319–330

    Article  PubMed  CAS  Google Scholar 

  122. Dickendesher T. L., Baldwin K. T., Mironova Y. A., Koriyama Y., Raiker S. J., Askew K. L., et al., NgR1 and NgR3 are receptors for chondroitin sulfate proteoglycans, Nat. Neurosci., 2012, 15, 703–712

    Article  PubMed  CAS  Google Scholar 

  123. Huber A. B., Weinmann O., Brosamle C., Oertle T., Schwab M. E., Patterns of Nogo mRNA and protein expression in the developing and adult rat and after CNS lesions, J. Neurosci., 2002, 22, 3553–3567

    PubMed  CAS  Google Scholar 

  124. Mekhail M., Almazan G., Tabrizian M., Oligodendrocyte-protection and remyelination post-spinal injuries: A review, Prog. Neurobiol., 2012, 96, 322–339

    Article  PubMed  CAS  Google Scholar 

  125. Mukhopadhyay G., Doherty P., Walsh F. S., Crocker P. R., Filbin M. T., A novel role for myelin-associated glycoprotein as an inhibitor of axonal regeneration, Neuron, 1994, 13, 757–767

    Article  PubMed  CAS  Google Scholar 

  126. McKerracher L., David S., Jackson D. L., Kottis V., Dunn R. J., Braun P. E., Identification of myelin-associated glycoprotein as a major myelin-derived inhibitor of neurite growth, Neuron, 1994, 13, 805–811

    Article  PubMed  CAS  Google Scholar 

  127. Prinjha R., Moore S. E., Vinson M., Blake S., Morrow R., Christie G., et al., Inhibitor of neurite outgrowth in humans, Nature, 2000, 403, 383–384

    Article  PubMed  CAS  Google Scholar 

  128. Moreau-Fauvarque C., Kumanogoh A., Camand E., Jaillard C., Barbin G., Boquet I., et al., The transmembrane semaphoring Sema4D/CD100, an inhibitor of axonal growth, is expressed on oligodendrocytes and upregulated after CNS lesion, J. Neurosci., 2003, 23, 9229–9239

    PubMed  CAS  Google Scholar 

  129. Benson M. D., Romero M. I., Lush M.E., Lu Q. R., Henkemeyer M., Parada L. F., Ephrin-B3 is a myelin-based inhibitor of neurite outgrowth, Proc. Natl. Acad. Sci. USA, 2005, 102, 10694–10699

    Article  PubMed  CAS  Google Scholar 

  130. Fournier A. E., Grandpre T., Strittmatter S. M., Identification of a receptor mediating Nogo-66 inhibition of axonal regeneration, Nature, 2001, 409, 341–346

    Article  PubMed  CAS  Google Scholar 

  131. Atwal J. K., Pinkston-Gosse J., Syken J., Stawicki S, Wu Y., Shatz C., et al., PirB is a functional receptor for myelin inhibitors of axonal regeneration, Science, 2008, 322, 967–970

    Article  PubMed  CAS  Google Scholar 

  132. Fujita Y., Endo S., Takai T., Yamashita T., Myelin suppresses axon regeneration by PIR-B/SHP-mediated inhibition of Trk activity, EMBO J., 2011, 1389–1401

  133. Fujita Y., Takashima R., Endo S., Takai T., Yamashita T., The p75 receptor mediates axon growth inhibition through an association with PIR-B, Cell Death Dis., 2011, 2, e198

    Article  PubMed  CAS  Google Scholar 

  134. Nakamura Y., Fujita Y., Ueno M., Takai T., Yamashita T., Paired immunoglobulin-like receptor B knockout does not enhance axonal regeneration or locomotor recovery after spinal cord injury, J. Biol. Chem., 2011, 286, 1876–1883

    Article  PubMed  CAS  Google Scholar 

  135. Hunt D, Coffin R. S., Anderson P. N., The Nogo receptor, its ligands and axonal regeneration in the spinal cord: a review, J. Neurocytol., 2002, 31, 93–120

    Article  PubMed  CAS  Google Scholar 

  136. Domeniconi M., Cao Z., Spencer T., Sivasankaran R., Wang K., Nikulina E., et al., Myelin-associated glycoprotein interacts with the Nogo66 receptor to inhibit neurite outgrowth, Neuron, 2002, 35, 283–290

    Article  PubMed  CAS  Google Scholar 

  137. Liu B. P., Fournier A., Grandpre T., Strittmatter S. M., Myelinassociated glycoprotein as a functional ligand for the Nogo-66 receptor, Science, 2002, 297, 1190–1193

    Article  PubMed  CAS  Google Scholar 

  138. Wang K., Koprivica V., Kim J. A., Sivasankaran R., Guo Y., Neve R. L., et al., Oligodendrocyte-myelin glycoprotein is a Nogo receptor ligand that inhibits neurite outgrowth, Nature, 2002, 417, 941–944

    Article  PubMed  CAS  Google Scholar 

  139. Wang K. C., Kim J. A., Sivasankaran R., Segal R., He Z., P75 interacts with the Nogo receptor as a co-receptor for Nogo, MAG and Omgp, Nature, 2002, 420, 74–78

    Article  CAS  Google Scholar 

  140. Park J. B., Yiu G., Kaneko S., Wang J., Chang J., He X., et al., A TNF receptor family member, TROY, is a coreceptor with Nogo receptor in mediating the inhibitory activity of myelin inhibitors, Neuron, 2005, 45, 345–351

    Article  PubMed  CAS  Google Scholar 

  141. Shao Z., Browning J. L., Lee X., Scott M. L., Shulga-Morskaya S., Allaire N., et al., TAJ/TROY, an orphan TNF receptor family member, binds Nogo-66 receptor 1 and regulates axonal regeneration, Neuron, 2005, 45, 353–359

    Article  PubMed  CAS  Google Scholar 

  142. Mi S., Troy/Taj and its role in CNS axon regeneration, Cytokine Growth Factor Rev., 2008, 19, 245–251

    Article  PubMed  CAS  Google Scholar 

  143. Mi S., Sandrock A., Miller R. H., LINGO-1 and its role in CNS repair, Int. J. Biochem. Cell Biol., 2008, 40, 1971–1978

    Article  PubMed  CAS  Google Scholar 

  144. Zhang Z., Xu X., Zhang Y., Zhou J., Yu Z., He C., LINGO-1 interacts with WNK1 to regulate nogo-induced inhibition of neurite extension, J. Biol. Chem., 2009, 284, 15717–15728

    Article  PubMed  CAS  Google Scholar 

  145. Bourikas D., Mir A., Walmsley A. R., LINGO-1-mediated inhibition of oligodendrocyte differentiation does not require the leucinerich repeats and is reversed by p75(NTR) antagonists, Mol. Cell. Neurosci., 2010, 45, 363–369

    Article  PubMed  CAS  Google Scholar 

  146. Yamagata T., Saito H., Habuchi O., Suzuki S., Purification and properties of bacterial chondroitinases and chondrosulfatases, J. Biol. Chem., 1968, 243, 1523–1535

    PubMed  CAS  Google Scholar 

  147. Suzuki S., Saito H., Yamagata T., Anno K., Seno N., Kawai Y., et al., Formation of three types of disulfated disaccharides from chondroitin sulfates by chondroitinase digestion, J. Biol. Chem., 1968, 243, 1543–1550

    PubMed  CAS  Google Scholar 

  148. Koppe G., Bruckner G., Hartig W., Delpech B., Bigl V., Characterization of proteoglycan-containing perineuronal nets by enzymatic treatments of rat brain sections, Histochem. J., 1997, 29, 11–20

    Article  PubMed  CAS  Google Scholar 

  149. Bruckner G., Bringmann A., Hartig W., Koppe G., Delpech B., Brauer K., Acute and long-lasting changes in extracellular-matrix chondroitinsulphate proteoglycans induced by injection of chondroitinase ABC in the adult rat brain, Exp. Brain Res., 1998, 121, 300–310

    Article  PubMed  CAS  Google Scholar 

  150. McKeon R. J., Hoke A., Silver J., Injury-induced proteoglycans inhibit the potential for laminin-mediated axon growth on astrocytic scars, Exp. Neurol., 1995, 136, 32–43

    Article  PubMed  CAS  Google Scholar 

  151. Bradbury E. J., Moon L. D. F., Popat R. J., King V. R., Bennett G. S., Patel P.N., et al., Chondroitinase ABC promotes functional recovery after spinal cord injury, Nature, 2002, 416, 636–640

    Article  PubMed  CAS  Google Scholar 

  152. Massey J. M., Hubscher C. H., Wagoner M. R., Decker J. A., Amps J., Silver J., et al., Chondroitinase ABC digestion of the perineuronal net promotes functional collateral sprouting in the cuneate nucleus after cervical spinal cord injury, J. Neurosci., 2006, 26, 4406–4414

    Article  PubMed  CAS  Google Scholar 

  153. Wang D., Ichiyama R. M., Zhao R., Andrews M. R., Fawcett J. W., Chondroitinase combined with rehabilitation promotes recovery of forelimb function in rats with chronic spinal cord injury, J. Neurosci., 2011, 31, 9332–9344

    Article  PubMed  CAS  Google Scholar 

  154. Garcia-Alias G., Barkhuysen S., Buckle M., Fawcett J. W., Chondroitinase ABC treatment opens a window of opportunity for task-specific rehabilitation, Nat. Neurosci., 2009, 12, 1145–1151

    Article  PubMed  CAS  Google Scholar 

  155. Tester N. J., Howland D. R., Chondroitinase ABC improves basic and skilled locomotion in spinal cord injured cats, Exp. Neurol., 2008, 209, 483–496

    Article  PubMed  CAS  Google Scholar 

  156. Liebscher T., Schnell L., Schnell D., Scholl J., Schneider R., Gullo M., et al., Nogo-A antibody improves regeneration and locomotion of spinal cord-injured rats, Ann. Neurol., 2005, 58, 706–719

    Article  PubMed  CAS  Google Scholar 

  157. Fouad K., Klusman I., Schwab M. E., Regenerating corticospinal fibers in the Marmoset (Callitrix jacchus) after spinal cord lesion and treatment with the anti-Nogo-A antibody IN-1, Eur. J. Neurosci., 2004, 20, 2479–2482

    Article  PubMed  CAS  Google Scholar 

  158. Freund P., Schmidlin E., Wannier T., Bloch J., Mir A., Schwab M. E., et al., Nogo-A-specific antibody treatment enhances sprouting and functional recovery after cervical lesion in adult primates, Nat. Med., 2006, 12, 790–792

    Article  PubMed  CAS  Google Scholar 

  159. Freund P., Wannier T., Schmidlin E., Bloch J., Mir A., Schwab M. E., et al., Anti-Nogo-A antibody treatment enhances sprouting of corticospinal axons rostral to a unilateral cervical spinal cord lesion in adult macaque monkey, J. Comp. Neurol., 2007, 502, 644–659

    Article  PubMed  CAS  Google Scholar 

  160. Grandpre T., Li S., Strittmatter S. M., Nogo-66 receptor antagonist peptide promotes axonal regeneration, Nature, 2002, 417, 547–551

    Article  PubMed  CAS  Google Scholar 

  161. Cao Y., Shumsky J. S., Sabol M. A., Kushner R. A., Strittmatter S., Hamers F. P., et al., 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, 2008, 22, 262–278

    Article  PubMed  CAS  Google Scholar 

  162. Li S., Strittmatter S. M., Delayed systemic Nogo-66 receptor antagonist promotes recovery from spinal cord injury, J. Neurosci., 2003, 23, 4219–4227

    PubMed  CAS  Google Scholar 

  163. Steward O., Sharp K, Yee K. M., Hofstadter M., A re-assessment of the effects of a Nogo-66 receptor antagonist on regenerative growth of axons and locomotor recovery after spinal cord injury in mice, Exp. Neurol., 2008, 209, 446–468

    Article  PubMed  CAS  Google Scholar 

  164. Zai L., Ferrari C., Dice C., Subbaiah S., Havton L. A., Coppola G., et al., Inosine augments the effects of a nogo receptor blocker and of environmental enrichment to restore skilled forelimb use after stroke, J. Neurosci., 2011, 31, 5977–5988

    Article  PubMed  CAS  Google Scholar 

  165. Zorner B., Schwab M. E., Anti-Nogo on the go: from animal models to a clinical trial, Ann. NY Acad. Sci., 2010, 1198(Suppl. 1), E22–E34

    Article  PubMed  Google Scholar 

  166. Yue Y., Su J., Cerretti D. P., Fox G. M., Jing S., Zhou R., Selective inhibition of spinal cord neurite outgrowth and cell survival by the Eph family ligand ephrin-A5, J. Neurosci., 1999, 19, 10026–10035

    PubMed  CAS  Google Scholar 

  167. Wahl S., Barth H., Ciossek T., Aktories K., Mueller B. K., Ephrin-A5 induces collapse of growth cones by activating Rho and Rho kinase, J. Cell Biol., 2000, 149, 263–270

    Article  PubMed  CAS  Google Scholar 

  168. Goldshmit Y., Spanevello M. D., Tajouri S., Li L., Rogers F., Pearse M., et al., EphA4 blockers promote axonal regeneration and functional recovery following spinal cord injury in mice, PLoS One, 2011, 6, e24636

    Article  PubMed  CAS  Google Scholar 

  169. Fabes J., Anderson P., Brennan C., Bolsover S., Regeneration-enhancing effects of EphA4 blocking peptide following corticospinal tract injury in adult rat spinal cord, Eur. J. Neurosci., 2007, 26, 2496–2505

    Article  PubMed  Google Scholar 

  170. Permentier-Batteur S., Finger E. N., Krishnan R., Rajapakse H. A., Sanders J. M., Kandpal G., et al., Attenuation of scratch-induced reactive astrogliosis by novel EphA4 kinase inhibitors, J. Neurochem., 2011, 118, 1016–1031

    Article  CAS  Google Scholar 

  171. Jin Y., Fischer I., Tessler A., Houle J. D., Transplants of fibroblasts genetically modified to express BDNF promote axonal regeneration from supraspinal neurons following chronic spinal cord injury, Exp. Neurol., 2002, 177, 265–275

    Article  PubMed  CAS  Google Scholar 

  172. Liu Y., Himes B. T., Murray M., Tessler A., Fischer I., Grafts of BDNFproducing fibroblasts rescue axotomized rubrospinal neurons and prevent their atrophy, Exp. Neurol., 2002, 178, 150–164

    Article  PubMed  CAS  Google Scholar 

  173. Tobias C. A., Shumsky J. S., Shibata M., Tuszynski M. H., Fischer I., Tessler A., et al., Delayed grafting of BDNF and NT-3 producing fibroblasts into the injured spinal cord stimulates sprouting, partially rescues axotomized red nucleus neurons from loss and atrophy, and provides limited regeneration, Exp. Neurol., 2003, 184, 97–113

    Article  PubMed  CAS  Google Scholar 

  174. Boyce V. S., Park J., Gage F. H., Mendell L. M., Differential effects of brainderived neurotrophic factor and neurotropin-3 on hindlimb function in paraplegic rats, Eur. J. Neurosci., 2012, 35, 221–232

    Article  PubMed  Google Scholar 

  175. White R. E., Yin F. Q., Jakeman L. B., TGF-alpha increases astrocyte invasion and promotes axonal growth into the lesion following spinal cord injury in mice, Exp. Neurol., 2008, 214, 10–24

    Article  PubMed  CAS  Google Scholar 

  176. White R. E., Rao M., Gensel J. C., McTigue D. M., Kaspar B. K., Jakeman L. B., Transforming growth factor alpha transforms astrocytes to a growth-supportive phenotype after spinal cord injury, J. Neurosci. 2011, 31, 15173–15187

    Article  PubMed  CAS  Google Scholar 

  177. Minnich J. E., Mann S. L., Stock M., Stolzenbach K. A., Mortell B. M., Soderstrom K. E., et al., Glial cell line-derived neurotrophic factor (GDNF) gene delivery protects cortical neurons from dying following a traumatic brain injury, Restor. Neurol. Neurosci., 2010, 28, 293–309

    PubMed  CAS  Google Scholar 

  178. DeGeorge M. L., Marlowe D., Werner E, Soderstrom K. E., Stock M, Mueller A., et al., Combining glial cell line-derived neurotrophic factor gene delivery (AdGNDF) with L-arginine decreases contusion size but not behavioral deficits after traumatic brain injury, Brain Res., 2011, 1403, 45–56

    Article  PubMed  CAS  Google Scholar 

  179. Monfils M. H., Driscoll I., Kamitakahara H., Wilson B., Flynn C, Teskey G. C., et al., FGF-2-induced cell proliferation stimulates anatomical, neurophysiological and functional recovery from neonatal motor cortex injury, Eur. J. Neurosci., 2006, 24, 739–749

    Article  PubMed  Google Scholar 

  180. Nemati F., Kolb B., FGF-2 induces behavioral recovery after early adolescent injury to the motor cortex of rats, Behav. Brain Res., 2011, 225, 184–191

    Article  PubMed  CAS  Google Scholar 

  181. Russell J. C., Szuflita N., Khatri R., Laterra J., Hossain M. A., Transgenic expression of human FGF-1 protects against hypoxic-ischemic injury in perinatal brain by intervening at caspase-XIAP signaling cascades, Neurobiol. Dis., 2006, 22, 677–690

    Article  PubMed  CAS  Google Scholar 

  182. Ming G. L., Song H., Adult neurogenesis in the mammalian central nervous system, Annu. Rev. Neurosci., 2005, 28, 223–250

    Article  PubMed  CAS  Google Scholar 

  183. Cameron H. A., Dayer A. G., New interneurons in the adult neocortex: small, sparse, but significant?, Biol. Psychiatry, 2008, 63, 650–655

    Article  PubMed  Google Scholar 

  184. Palmer T. D., Markakis E. A., Willhoite A. R., Safar F., Gage F. H., Fibroblast growth factor-2 activates a latent neurogenic program in neural stem cells from diverse regions of the adult CNS, J. Neurosci., 1999, 19, 8487–8497

    PubMed  CAS  Google Scholar 

  185. Homman-Ludiye J., Merson T., Bourne J., The early postnatal nonhuman primate neocortex contains self-renewing multipotent neural progenitor cells, PLoS One, 2012, 7, e34383

    Article  PubMed  CAS  Google Scholar 

  186. Arsenijevic Y., Villemure J. G., Brunet J. F., Bloch J. J., Deglon N., Kostic C., et al., Isolation of multipotent neural precursors residing in the cortex of the adult human brain, Exp. Neurol., 2001, 170, 48–62

    Article  PubMed  CAS  Google Scholar 

  187. Arellano J. I., Rakic P., Neuroscience: gone with the wean, Nature, 2011, 478, 333–334

    Article  PubMed  CAS  Google Scholar 

  188. Sanai N, Nguyen T., Ihrie R. A., Mirzadeh Z., Tsai H. H., Wong M., et al., Corridors of migrating neurons in the human brain and their decline during infancy, Nature, 2011, 478, 382–386

    Article  PubMed  CAS  Google Scholar 

  189. Sidman R. L., Rakic P., Neuronal migration, with special reference to developing human brain: a review, Brain Res., 1973, 62, 1–35

    Article  PubMed  CAS  Google Scholar 

  190. Magavi S. S., Leavitt B. R., Macklis J. D., Induction of neurogenesis in the neocortex of adult mice, Nature, 2000, 405, 951–955

    Article  PubMed  CAS  Google Scholar 

  191. Buffo A., Rite I., Tripathi P., Lepier A., Colak D, Horn A. P., et al., Origin and progeny of reactive gliosis: A source of multipotent cells in the injured brain, Proc. Natl. Acad. Sci. USA, 2008, 105, 3581–3586

    Article  PubMed  CAS  Google Scholar 

  192. Rosenzweig E. S., Courtine G., Jindrich D. L., Brock J. H., Ferguson A. R., Strand S. C., et al., Extensive spontaneous plasticity of corticospinal projections after primate spinal cord injury, Nat. Neurosci., 2010, 13, 1505–1510

    Article  PubMed  CAS  Google Scholar 

  193. Vessal M., Aycock A., Garton M. T., Ciferri M., Darian-Smith C., Adult neurogenesis in primate and rodent spinal cord: comparing a cervical dorsal rhizotomy with a dorsal column transaction, Eur. J. Neurosci., 2007, 26, 2777–2794

    Article  PubMed  Google Scholar 

  194. Vessal M., Darian-Smith C., Adult neurogenesis occurs in primate sensorimotor cortex following cervical dorsal rhizotomy, J. Neurosci., 2010, 30, 8613–8623

    Article  PubMed  CAS  Google Scholar 

  195. Thuret S., Moon L. D., Gage F. H., Therapeutic interventions after spinal cord injury, Nat. Rev. Neurosci., 2006, 7, 628–643

    Article  PubMed  CAS  Google Scholar 

  196. Iwanami A., Kaneko S., Nakamura M, Kanemura Y., Mori H., Kobayashi S., et al., Transplantation of human neural stem cells for spinal cord injury in primates, J. Neurosci. Res., 2005, 80, 182–190

    Article  PubMed  CAS  Google Scholar 

  197. Daadi M. M., Davis A. S., Arac A., Li Z., Maag A. L., Bhatnagar R., et al., Human neural stem cell grafts modify microglial response and enhance axonal sprouting in neonatal hypoxic-ischemic brain injury, Stroke, 2010, 41, 516–523

    Article  PubMed  Google Scholar 

  198. Lee I. S., Jung K., Kim M., Park K. I., Neural stem cells: properties and therapeutic potentials for hypoxic-ischemic brain injury in newborn infants, Pediatr. Int., 2010, 52, 855–865

    Article  PubMed  Google Scholar 

  199. Siqueira R. C., Stem cell therapy for retinal diseases: update, Stem Cell Res. Ther., 2011, 2, 50

    Article  PubMed  CAS  Google Scholar 

  200. Burns T. C., Verfaillie C. M., Low W. C., Stem cells for ischemic brain injury: a critical review, J. Comp. Neurol., 2009, 515, 125–144

    Article  PubMed  Google Scholar 

  201. Dong J., Liu B., Song L., Lu L., Xu H., Gu Y., Neural stem cells in the ischemic and injured brain: endogeneous and transplanted, Cell Tissue Bank., 2011, [Epub ahead of print]

  202. Jiang J. Bu X., Liu M., Cheng P., Transplantation of autologous bonemarrow- derived mesenchymal stem cells for traumatic brain injury, Neural Regener. Res., 2012, 7, 46–53

    Google Scholar 

  203. Haas S., Weidner N., Winkler J., Adult stem cell therapy in stroke, Curr. Opin. Neurol., 2005, 18, 59–64

    Article  PubMed  Google Scholar 

  204. Hu S.-L., Luo H.-S., Li J.-T., Xia Y.-Z., Li L., Zhang L.-J., et al., Functional recovery in acute traumatic spinal cord injury after transplantation of human umbilical cord mesenchymal stem cells, Crit. Care Med., 2010, 38, 2181–2189

    Article  PubMed  Google Scholar 

  205. Bretzner F., Gilbert F., Baylis F., Brownstone R. M., Target populations for first-in-human embryonic stem cell research in spinal cord injury, Cell Stem Cell, 2011, 8, 468–475

    Article  PubMed  CAS  Google Scholar 

  206. Wirth E. 3rd, Lebkowski J. S., Lebacqz K, Response to Frederic Bretzner et al. “Target populations for first-in-human embryonic stem cell research in spinal cord injury”, Cell Stem Cell, 2011, 8, 476–478

    Article  PubMed  CAS  Google Scholar 

  207. Brown E., Economics, not science, thwarts embryonic stem cell therapy, LA Times, 21 Nov. 2011

  208. Kondziolka D., Wechsler L., Stroke repair with cell transplantation: neuronal cells, neuroprogenitor cells, and stem cells, Neurosurg. Focus, 2008, 24, e13

    Article  PubMed  Google Scholar 

  209. Harkema S. J., Neural plasticity after human spinal cord injury: application of locomotor training to the rehabilitation of walking, Neuroscientist, 2001, 7, 455–468

    Article  PubMed  CAS  Google Scholar 

  210. Nelles G., Esser J., Eckstein A., Tiede A., Gerhard H., Diener H. C., Compensatory visual field training for patients with hemianopia after stroke, Neurosci. Lett., 2001, 306, 189–192

    Article  PubMed  CAS  Google Scholar 

  211. Das A., Huxlin K. R., New approaches to visual rehabilitation for cortical blindness: outcomes and putative mechanisms, Neuroscientist, 2010, 16, 374–387

    Article  PubMed  Google Scholar 

  212. Trauzettel-Klosinski S., Current methods of visual rehabilitation, Dtsch. Arztebl. Int., 2011, 108, 871–878

    PubMed  Google Scholar 

  213. Schnell L., Hunanyan A. S., Bowers W. J., Horner P. J., Federoff H. J., Gullo M., et al., 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, 1256–1267

    Article  PubMed  Google Scholar 

  214. Garcia-Alias G., Petrosyan H. A., Schnell L., Horner P. J., Bowers W. J., Mendell L. M., et al., Chondroitinase ABC combined with neurotrophin NT-3 secretion and NR2D expression promotes axonal plasticity and functional recovery in rats with lateral hemisection of the spinal cord, J. Neurosci., 2011, 31, 17788–17799

    Article  PubMed  CAS  Google Scholar 

  215. Arvanian V. L., Bowers W. J., Anderson A., Horner P. J., Federoff H. J, Mendell L. M., Combined delivery of neurotrophin-3 and NMDA receptors 2D subunit strengthens synaptic transmission in contused and staggered double hemisected spinal cord of neonatal rat, Exp. Neurol., 2006, 197, 347–352

    Article  PubMed  CAS  Google Scholar 

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Teo, L., Rosenfeld, J.V. & Bourne, J.A. Models of CNS injury in the nonhuman primate: A new era for treatment strategies. Translat.Neurosci. 3, 181–195 (2012). https://doi.org/10.2478/s13380-012-0023-z

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