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Neural Plasticity
Volume 2014, Article ID 451639, 16 pages
http://dx.doi.org/10.1155/2014/451639
Research Article

Behavioral Improvement and Regulation of Molecules Related to Neuroplasticity in Ischemic Rat Spinal Cord Treated with PEDF

Neuroregeneration Center, Department of Neurology, School of Medicine, University of São Paulo, Avenida Dr. Arnaldo 455, 2nd Floor, Room 2119, 01246-903-São Paulo, SP, Brazil

Received 22 December 2013; Revised 4 June 2014; Accepted 5 June 2014; Published 3 July 2014

Academic Editor: Leszek Kaczmarek

Copyright © 2014 Chary Marquez Batista et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. M. M. Bilak, S. Patricia Becerra, A. M. Vincent, B. H. Moss, M. S. Aymerich, and R. W. Kuncl, “Identification of the neuroprotective molecular region of pigment epithelium-derived factor and its binding sites on motor neurons,” Journal of Neuroscience, vol. 22, no. 21, pp. 9378–9386, 2002. View at Google Scholar · View at Scopus
  2. M. M. Bilak, A. M. Corse, S. R. Bilak, M. Lehar, J. Tombran-Tink, and R. W. Kuncl, “Pigment epithelium-derived factor (PEDF) protects motor neurons from chronic glutamate-mediated neurodegeneration,” Journal of Neuropathology and Experimental Neurology, vol. 58, no. 7, pp. 719–728, 1999. View at Publisher · View at Google Scholar · View at Scopus
  3. D. W. Dawson, O. V. Volpert, P. Gillis et al., “Pigment epithelium-derived factor: a potent inhibitor of angiogenesis,” Science, vol. 285, no. 5425, pp. 245–248, 1999. View at Publisher · View at Google Scholar · View at Scopus
  4. N. I. Minkevich, V. M. Lipkin, and I. A. Kostanyan, “PEDF—a noninhibitory serpin with neurotrophic activity,” Acta Naturae, vol. 2, pp. 62–71, 2010. View at Google Scholar
  5. T. Yabe, J. T. Herbert, A. Takanohashi, and J. P. Schwartz, “Treatment of cerebellar granule cell neurons with the neurotrophic factor pigment epithelium-derived factor in vitro enhances expression of other neurotrophic factors as well as cytokines and chemokines,” Journal of Neuroscience Research, vol. 77, no. 5, pp. 642–652, 2004. View at Publisher · View at Google Scholar · View at Scopus
  6. V. Dietz and K. Fouad, “Restoration of sensorimotor functions after spinal cord injury,” Brain, vol. 137, part 3, pp. 654–667, 2013. View at Google Scholar
  7. Z. Liu, M. Chopp, X. Ding, Y. Cui, and Y. Li, “Axonal remodeling of the Corticospinal tract in the spinal cord contributes to voluntary motor recovery after stroke in adult mice,” Stroke, vol. 44, no. 7, pp. 1951–1956, 2013. View at Publisher · View at Google Scholar · View at Scopus
  8. S. Rossignol, G. Barriere, O. Alluin, and A. Frigon, “Re-expression of locomotor function after partial spinal cord injury,” Physiology, vol. 24, no. 2, pp. 127–139, 2009. View at Publisher · View at Google Scholar · View at Scopus
  9. S. C. L. Telles, R. C. Alves, and G. Chadi, “Periodic limb movements during sleep and restless legs syndrome in patients with ASIA A spinal cord injury,” Journal of the Neurological Sciences, vol. 303, no. 1-2, pp. 119–123, 2011. View at Publisher · View at Google Scholar · View at Scopus
  10. S. C. L. Telles, R. S. C. Alves, and G. Chadi, “Spinal cord injury as a trigger to develop periodic leg movements during sleep: an evolutionary perspective,” Arquivos de Neuro-Psiquiatria, vol. 70, no. 11, pp. 880–884, 2012. View at Publisher · View at Google Scholar · View at Scopus
  11. G. Barrière, H. Leblond, J. Provencher, and S. Rossignol, “Prominent role of the spinal central pattern generator in the recovery of locomotion after partial spinal cord injuries,” Journal of Neuroscience, vol. 28, no. 15, pp. 3976–3987, 2008. View at Publisher · View at Google Scholar · View at Scopus
  12. V. S. Boyce, J. Park, F. H. Gage, and L. M. Mendell, “Differential effects of brain-derived neurotrophic factor and neurotrophin-3 on hindlimb function in paraplegic rats,” European Journal of Neuroscience, vol. 35, no. 2, pp. 221–232, 2012. View at Publisher · View at Google Scholar · View at Scopus
  13. R. Puttagunta and S. di Giovanni, “Retinoic acid signaling in axonal regeneration,” Frontiers in Molecular Neuroscience, vol. 4, p. 59, 2012. View at Publisher · View at Google Scholar · View at Scopus
  14. S. Zong, G. Zeng, B. Wei, C. Xiong, and Y. Zhao, “Beneficial effect of interleukin-1 receptor antagonist protein on spinal cord injury recovery in the rat,” Inflammation, vol. 35, no. 2, pp. 520–526, 2012. View at Publisher · View at Google Scholar · View at Scopus
  15. Q. Chen and H. D. Shine, “Neuroimmune processes associated with Wallerian degeneration support neurotrophin-3-induced axonal sprouting in the injured spinal cord,” Journal of Neuroscience Research, vol. 91, no. 10, pp. 1280–1291, 2013. View at Publisher · View at Google Scholar · View at Scopus
  16. K. D. Dougherty, C. F. Dreyfus, and I. B. Black, “Brain-derived neurotrophic factor in astrocytes, oligodendrocytes, and microglia/macrophages after spinal cord injury,” Neurobiology of Disease, vol. 7, no. 6, pp. 574–585, 2000. View at Publisher · View at Google Scholar · View at Scopus
  17. M. Shinozaki, M. Nakamura, T. Konomi et al., “Distinct roles of endogenous vascular endothelial factor receptor 1 and 2 in neural protection after spinal cord injury,” Neuroscience Research, vol. 78, pp. 55–64, 2014. View at Google Scholar
  18. M. S. R. Andrade, L. M. Mendonça, and G. Chadi, “Treadmill running protects spinal cord contusion from secondary degeneration,” Brain Research, vol. 1346, pp. 266–278, 2010. View at Publisher · View at Google Scholar · View at Scopus
  19. F. P. Guzen, R. J. De Almeida Leme, M. S. R. De Andrade, B. A. De Luca And, and G. Chadi, “Glial cell line-derived neurotrophic factor added to a sciatic nerve fragment grafted in a spinal cord gap ameliorates motor impairments in rats and increases local axonal growth,” Restorative Neurology and Neuroscience, vol. 27, no. 1, pp. 1–16, 2009. View at Publisher · View at Google Scholar · View at Scopus
  20. G. Chadi, A. Moller, L. Rosen et al., “Protective actions of human recombinant basic fibroblast growth factor on MPTP-lesioned nigrostriatal dopamine neurons after intraventricular infusion,” Experimental Brain Research, vol. 97, no. 1, pp. 145–158, 1993. View at Google Scholar · View at Scopus
  21. B. J. Dickson, “Molecular mechanisms of axon guidance,” Science, vol. 298, no. 5600, pp. 1959–1964, 2002. View at Publisher · View at Google Scholar · View at Scopus
  22. I. Dudanova, T. Kao, J. E. Herrmann, B. Zheng, A. Kania, and R. Klein, “Genetic evidence for a contribution of EphA:EphrinA reverse signaling to motor axon guidance,” The Journal of Neuroscience, vol. 32, no. 15, pp. 5209–5215, 2012. View at Publisher · View at Google Scholar · View at Scopus
  23. M. Luxey, T. Jungas, J. Laussu, C. Audouard, A. Garces, and A. Davy, “Eph:ephrin-B1 forward signaling controls fasciculation of sensory and motor axons,” Developmental Biology, vol. 383, no. 2, pp. 264–274, 2013. View at Publisher · View at Google Scholar
  24. J. Aoto and L. Chen, “Bidirectional ephrin/Eph signaling in synaptic functions,” Brain Research, vol. 1184, no. 1, pp. 72–80, 2007. View at Publisher · View at Google Scholar · View at Scopus
  25. M. Henkemeyer, O. S. Itkis, M. Ngo, P. W. Hickmott, and I. M. Ethell, “Multiple EphB receptor tyrosine kinases shape dendritic spines in the hippocampus,” The Journal of Cell Biology, vol. 163, no. 6, pp. 1313–1326, 2003. View at Publisher · View at Google Scholar · View at Scopus
  26. L. Zhou, S. J. Martinez, M. Haber et al., “EphA4 signaling regulates phospholipase Cγ1 activation, cofilin membrane association, and dendritic spine morphology,” Journal of Neuroscience, vol. 27, no. 19, pp. 5127–5138, 2007. View at Publisher · View at Google Scholar · View at Scopus
  27. W. Li, Z. Zheng, and J. Keifer, “Transsynaptic EphB/Ephrin-B signaling regulates growth of presynaptic boutons required for classical conditioning,” Journal of Neuroscience, vol. 31, no. 23, pp. 8441–8449, 2011. View at Publisher · View at Google Scholar · View at Scopus
  28. T. B. Puschmann and A. M. Turnley, “Eph receptor tyrosine kinases regulate astrocyte cytoskeletal rearrangement and focal adhesion formation,” Journal of Neurochemistry, vol. 113, no. 4, pp. 881–894, 2010. View at Publisher · View at Google Scholar · View at Scopus
  29. Z. Ren, X. Chen, J. Yang et al., “Improved axonal regeneration after spinal cord injury in mice with conditional deletion of ephrin B2 under the GFAP promoter,” Neuroscience, vol. 241, pp. 89–99, 2013. View at Publisher · View at Google Scholar · View at Scopus
  30. M. L. Bochenek, S. Dickinson, J. W. Astin, R. H. Adams, and C. D. Nobes, “Ephrin-B2 regulates endothelial cell morphology and motility independently of Eph-receptor binding,” Journal of Cell Science, vol. 123, no. 8, pp. 1235–1246, 2010. View at Publisher · View at Google Scholar · View at Scopus
  31. L. Q. Bundesen, T. A. Scheel, B. S. Bregman, and L. F. Kromer, “Ephrin-B2 and EphB2 regulation of astrocyte-meningeal fibroblast interactions in response to spinal cord lesions in adult rats,” Journal of Neuroscience, vol. 23, no. 21, pp. 7789–7800, 2003. View at Google Scholar · View at Scopus
  32. N. J. Xu and M. Henkemeyer, “Ephrin reverse signaling in axon guidance and synaptogenesis,” Seminars in Cell & Developmental Biology, vol. 23, no. 1, pp. 58–64, 2012. View at Publisher · View at Google Scholar · View at Scopus
  33. C. D. Nandini, N. Itoh, and K. Sugahara, “Novel 70-kDa chondroitin sulfate/dermatan sulfate hybrid chains with a unique heterogenous sulfation pattern from shark skin, which exhibit neuritogenic activity and binding activities for growth factors and neurotrophic factors,” Journal of Biological Chemistry, vol. 280, no. 6, pp. 4058–4069, 2005. View at Publisher · View at Google Scholar · View at Scopus
  34. M. Inatani, H. Tanihara, A. Oohira, M. Honjo, and Y. Honda, “Identification of a nervous tissue-specific chondroitin sulfate proteoglycan, neurocan, in developing rat retina,” Investigative Ophthalmology & Visual Science, vol. 40, no. 10, pp. 2350–2359, 1999. View at Google Scholar · View at Scopus
  35. A. Oohira, F. Matsui, E. Watanabe, Y. Kushima, and N. Maeda, “Developmentally regulated expression of a brain specific species of chondroitin sulfate proteoglycan, neurocan, identified with a monoclonal antibody 1G2 in the rat cerebrum,” Neuroscience, vol. 60, no. 1, pp. 145–157, 1994. View at Publisher · View at Google Scholar · View at Scopus
  36. D. K. Anderson and E. D. Hall, “Pathophysiology of spinal cord trauma,” Annals of Emergency Medicine, vol. 22, no. 6, pp. 987–992, 1993. View at Publisher · View at Google Scholar · View at Scopus
  37. J. W. Rowland, G. W. J. Hawryluk, B. Kwon, and M. G. Fehlings, “Current status of acute spinal cord injury pathophysiology and emerging therapies: promise on the horizon,” Neurosurgical Focus, vol. 25, no. 5, p. E2, 2008. View at Google Scholar · View at Scopus
  38. M. Gaviria, H. Haton, F. Sandillon, and A. Privat, “A mouse model of acute ischemic spinal cord injury,” Journal of Neurotrauma, vol. 19, no. 2, pp. 205–221, 2002. View at Publisher · View at Google Scholar · View at Scopus
  39. B. D. Watson, “Evaluation of the concomitance of lipid peroxidation in experimental models of cerebral ischemia and stroke,” Progress in Brain Research, vol. 96, pp. 69–95, 1993. View at Publisher · View at Google Scholar · View at Scopus
  40. A. S. Rivlin and C. H. Tator, “Objective clinical assessment of motor function after experimental spinal cord injury in the rat,” Journal of Neurosurgery, vol. 47, no. 4, pp. 577–581, 1977. View at Publisher · View at Google Scholar · View at Scopus
  41. M. G. Fehlings and C. H. Tator, “The relationships among the severity of spinal cord injury, residual neurological function, axon counts, and counts of retrogradely labeled neurons after experimental spinal cord injury,” Experimental Neurology, vol. 132, no. 2, pp. 220–228, 1995. View at Publisher · View at Google Scholar · View at Scopus
  42. J. Sedy, L. Urdzikova, P. Jendelova, and E. Sykova, “Methods for behavioral testing of spinal cord injured rats,” Neuroscience & Biobehavioral Reviews, vol. 32, pp. 550–580, 2008. View at Google Scholar
  43. G. Chadi, L. Rosen, A. Cintra et al., “Corticosterone increases FGF-2 (bFGF) immunoreactivity in the substantia nigra of the rat,” NeuroReport, vol. 4, no. 6, pp. 783–786, 1993. View at Publisher · View at Google Scholar · View at Scopus
  44. G. Chadi, B. Tinner, L. F. Agnati, and K. Fuxe, “Basic fibroblast growth factor (bFGF, FGF-2) immunoreactivity exists in the noradrenaline, adrenaline and 5-HT nerve cells of the rat brain,” Neuroscience Letters, vol. 160, no. 2, pp. 171–176, 1993. View at Publisher · View at Google Scholar · View at Scopus
  45. G. Paxinos and C. Watson, The Rat Brain: In Stereotaxic Coordinates, Harcourt Brace Jovanovich, San Diego, Calif, USA, 1986.
  46. V. C. Gomide and G. Chadi, “Glial bFGF and S100 immunoreactivities increase in ascending dopamine pathways following striatal 6-OHDA-induced partial lesion of the nigrostriatal system: a sterological analysis,” International Journal of Neuroscience, vol. 115, no. 4, pp. 537–555, 2005. View at Publisher · View at Google Scholar · View at Scopus
  47. R. W. P. Rodrigues, V. C. Gomide, and G. Chadi, “Astroglial and microglial reaction after a partial nigrostriatal degeneration induced by the striatal injection of different doses of 6-hydroxydopamine,” International Journal of Neuroscience, vol. 109, no. 1-2, pp. 91–126, 2001. View at Publisher · View at Google Scholar · View at Scopus
  48. M. S. R. Andrade, F. R. Hanania, K. Daci, R. J. A. Leme, and G. Chadi, “Contuse lesion of the rat spinal cord of moderate intensity leads to a higher time-dependent secondary neurodegeneration than severe one. An open-window for experimental neuroprotective interventions,” Tissue and Cell, vol. 40, no. 2, pp. 143–156, 2008. View at Publisher · View at Google Scholar · View at Scopus
  49. G. Chadi, M. S. R. Andrade, R. J. A. Leme, and V. C. Gomide, “Experimental models of partial lesion of rat spinal cord to investigate neurodegeneration, glial activation, and behavior impairments,” International Journal of Neuroscience, vol. 111, no. 3-4, pp. 137–165, 2001. View at Publisher · View at Google Scholar · View at Scopus
  50. J. Do Carmo Cunha, B. De Freitas Azevedo Levy, B. A. De Luca, M. S. R. De Andrade, V. C. Gomide, and G. Chadi, “Responses of reactive astrocytes containing S100β protein and fibroblast growth factor-2 in the border and in the adjacent preserved tissue after a contusion injury of the spinal cord in rats: Implications for wound repair and neuroregeneration,” Wound Repair and Regeneration, vol. 15, no. 1, pp. 134–146, 2007. View at Publisher · View at Google Scholar · View at Scopus
  51. G. Chadi, C. Silva, J. R. Maximino, K. Fuxe, and G. O. da Silva, “Adrenalectomy counteracts the local modulation of astroglial fibroblast growth factor system without interfering with the pattern of 6-OHDA-induced dopamine degeneration in regions of the ventral midbrain,” Brain Research, vol. 1190, no. 1, pp. 23–38, 2008. View at Publisher · View at Google Scholar · View at Scopus
  52. K. Korkmaz, H. S. Gedik, A. B. Budak et al., “Effect of heparin on neuroprotection against spinal cord ischemia and reperfusion in rats,” European Review for Medical and Pharmacological Sciences, vol. 17, no. 4, pp. 522–530, 2013. View at Google Scholar · View at Scopus
  53. J. Novy, A. Carruzzo, P. Maeder, and J. Bogousslavsky, “Spinal cord ischemia: clinical and imaging patterns, pathogenesis, and outcomes in 27 patients,” Archives of Neurology, vol. 63, no. 8, pp. 1113–1120, 2006. View at Publisher · View at Google Scholar · View at Scopus
  54. S. Salvador de la Barrera, A. Barca-Buyo, A. Montoto-Marqués, M. E. Ferreiro-Velasco, M. Cidoncha-Dans, and A. Rodriguez-Sotillo, “Spinal cord infarction: prognosis and recovery in a series of 36 patients,” Spinal Cord, vol. 39, no. 10, pp. 520–525, 2001. View at Publisher · View at Google Scholar · View at Scopus
  55. C. Temiz, I. Solmaz, O. Tehli et al., “The effects of splenectomy on lipid peroxidation and neuronal loss in experimental spinal cord ischemia/reperfusion injury,” Turkish Neurosurgery, vol. 23, no. 1, pp. 67–74, 2013. View at Publisher · View at Google Scholar · View at Scopus
  56. M. Oudega, “Molecular and cellular mechanisms underlying the role of blood vessels in spinal cord injury and repair,” Cell and Tissue Research, vol. 349, no. 1, pp. 269–288, 2012. View at Publisher · View at Google Scholar · View at Scopus
  57. R. B. Cecatto, J. R. Maximino, and G. Chadi, “Motor recovery and cortical plasticity after functional electrical stimulation in a rat model of focal stroke,” American Journal of Physical Medicine & Rehabilitation, 2014. View at Publisher · View at Google Scholar
  58. I. Cheng, R. E. Mayle, C. A. Cox et al., “Functional assessment of the acute local and distal transplantation of human neural stem cells after spinal cord injury,” The Spine Journal, vol. 12, no. 11, pp. 1040–1044, 2012. View at Publisher · View at Google Scholar · View at Scopus
  59. N. D. James, K. Bartus, J. Grist, D. L. H. Bennett, S. B. McMahon, and E. J. Bradbury, “Conduction failure following spinal cord injury: functional and anatomical changes from acute to chronic stages,” The Journal of Neuroscience, vol. 31, no. 50, pp. 18543–18555, 2011. View at Publisher · View at Google Scholar · View at Scopus
  60. T. Murakami, T. Kanchiku, H. Suzuki et al., “Anti-interleukin-6 receptor antibody reduces neuropathic pain following spinal cord injury in mice,” Experimental and Therapeutic Medicine, vol. 6, pp. 1194–1198, 2013. View at Google Scholar
  61. S. J. O'Carroll, C. A. Gorrie, S. Velamoor, C. R. Green, and L. F. B. Nicholson, “Connexin43 mimetic peptide is neuroprotective and improves function following spinal cord injury,” Neuroscience Research, vol. 75, no. 3, pp. 256–267, 2013. View at Publisher · View at Google Scholar · View at Scopus
  62. J. H. Park, J. Min, S. R. Baek, S. W. Kim, I. K. Kwon, and S. R. Jeon, “Enhanced neuroregenerative effects by scaffold for the treatment of a rat spinal cord injury with Wnt3a-secreting fibroblasts,” Acta Neurochirurgica, vol. 155, pp. 809–816, 2013. View at Publisher · View at Google Scholar · View at Scopus
  63. B. D. Watson, R. Prado, W. D. Dietrich, M. D. Ginsberg, and B. A. Green, “Photochemically induced spinal cord injury in the rat,” Brain Research, vol. 367, no. 1-2, pp. 296–300, 1986. View at Publisher · View at Google Scholar · View at Scopus
  64. J. X. Hao, P. Herregodts, G. Lind, B. Meyerson, A. Seiger, and Z. Wiesenfeld-Hallin, “Photochemically induced spinal cord ischaemia in rats: assessment of blood flow by laser Doppler flowmetry,” Acta Physiologica Scandinavica, vol. 151, no. 5, pp. 209–215, 1994. View at Google Scholar · View at Scopus
  65. R. Prado, W. D. Dietrich, B. D. Watson, M. D. Ginsberg, and B. A. Green, “Photochemically induced graded spinal cord infarction. Behavioral, electrophysiological, and morphological correlates,” Journal of Neurosurgery, vol. 67, no. 5, pp. 745–753, 1987. View at Publisher · View at Google Scholar · View at Scopus
  66. M. D. Ginsberg, Y. Castella, W. D. Dietrich, B. D. Watson, and R. Busto, “Acute thrombotic infarction suppresses metabolic activation of ipsilateral somatosensory cortex: Evidence for functional diaschisis,” Journal of Cerebral Blood Flow and Metabolism, vol. 9, no. 3, pp. 329–341, 1989. View at Publisher · View at Google Scholar · View at Scopus
  67. A. J. Hunter, A. R. Green, and A. J. Cross, “Animal models of acute ischaemic stroke: can they predict clinically successful neuroprotective drugs?” Trends in Pharmacological Sciences, vol. 16, no. 4, pp. 123–128, 1995. View at Publisher · View at Google Scholar · View at Scopus
  68. R. J. Traystman, “Animal models of focal and global cerebral ischemia,” ILAR Journal, vol. 44, no. 2, pp. 85–95, 2003. View at Publisher · View at Google Scholar · View at Scopus
  69. L. L. T. Bianqui, B. B. Zanon, C. M. Batista, M. M. A. A. Ivo, R. B. Cecatto, and G. Chadi, “Caracterization of photochemically induced low thoracic rat spinal cord injury and the neuroplasticity responses in lumbar anterior horn. Behavior, cellular and biochemical evaluations,” Submitted.
  70. P. A. Guertin, R. Ung, and P. Rouleau, “Oral administration of a tri-therapy for central pattern generator activation in paraplegic mice: proof-of-concept of efficacy,” Biotechnology Journal, vol. 5, no. 4, pp. 421–426, 2010. View at Publisher · View at Google Scholar · View at Scopus
  71. G. C. Koopmans, R. Deumens, W. M. M. Honig et al., “Functional recovery, serotonergic sprouting, and endogenous progenitor fates in response to delayed environmental enrichment after spinal cord injury,” Journal of Neurotrauma, vol. 29, no. 3, pp. 514–527, 2012. View at Publisher · View at Google Scholar · View at Scopus
  72. M. Martinez, H. Delivet-Mongrain, H. Leblond, and S. Rossignol, “Incomplete spinal cord injury promotes durable functional changes within the spinal locomotor circuitry,” Journal of Neurophysiology, vol. 108, no. 1, pp. 124–134, 2012. View at Publisher · View at Google Scholar · View at Scopus
  73. P. Freund, E. Schmidlin, T. Wannier et al., “Nogo-A-specific antibody treatment enhances sprouting and functional recovery after cervical lesion in adult primates,” Nature Medicine, vol. 12, pp. 790–792, 2006. View at Google Scholar
  74. P. Freund, T. Wannier, E. Schmidlin et al., “Anti-Nogo-A antibody treatment enhances sprouting of corticospinal axons rostral to a unilateral cervical spinal cord lesion in adult macaque monkey,” Journal of Comparative Neurology, vol. 502, no. 4, pp. 644–659, 2007. View at Publisher · View at Google Scholar · View at Scopus
  75. A. Blesch, H. Yang, N. Weidner, A. Hoang, and D. Otero, “Axonal responses to cellularly delivered NT-4/5 after spinal cord injury,” Molecular and Cellular Neuroscience, vol. 27, no. 2, pp. 190–201, 2004. View at Publisher · View at Google Scholar · View at Scopus
  76. C. Iannotti, Y. Ping Zhang, C. B. Shields, Y. Han, D. A. Burke, and X. Xu, “A neuroprotective role of glial cell line-derived neurotrophic factor following moderate spinal cord contusion injury,” Experimental Neurology, vol. 189, no. 2, pp. 317–332, 2004. View at Publisher · View at Google Scholar · View at Scopus
  77. P. J. Johnson, S. R. Parker, and S. E. Sakiyama-Elbert, “Controlled release of neurotrophin-3 from fibrin-based tissue engineering scaffolds enhances neural fiber sprouting following subacute spinal cord injury,” Biotechnology and Bioengineering, vol. 104, no. 6, pp. 1207–1214, 2009. View at Publisher · View at Google Scholar · View at Scopus
  78. M. G. Bowden, A. E. Embry, and C. M. Gregory, “Physical therapy adjuvants to promote optimization of walking recovery after stroke,” Stroke Research and Treatment, vol. 2011, Article ID 601416, 10 pages, 2011. View at Publisher · View at Google Scholar · View at Scopus
  79. E. M. F. Spangenberg, H. Augustsson, K. Dahlborn, B. Essén-Gustavsson, and K. Cvek, “Housing-related activity in rats: Effects on body weight, urinary corticosterone levels, muscle properties and performance,” Laboratory Animals, vol. 39, no. 1, pp. 45–57, 2005. View at Publisher · View at Google Scholar · View at Scopus
  80. G. V. W. Johnson and R. S. Jope, “The role of microtubule-associated protein 2 (MAP-2) in neuronal growth, plasticity, and degeneration,” Journal of Neuroscience Research, vol. 33, no. 4, pp. 505–512, 1992. View at Publisher · View at Google Scholar · View at Scopus
  81. D. Hockenbery, G. Nunez, C. Milliman, R. D. Schreiber, and S. J. Korsmeyer, “Bcl-2 is an inner mitochondrial membrane protein that blocks programmed cell death,” Nature, vol. 348, no. 6299, pp. 334–336, 1990. View at Publisher · View at Google Scholar · View at Scopus
  82. M. D. Jacobson, J. F. Burne, M. P. King, T. Miyashita, J. C. Reed, and M. C. Raff, “Bcl-2 blocks apoptosis in cells lacking mitochondrial DNA,” Nature, vol. 361, no. 6410, pp. 365–369, 1993. View at Publisher · View at Google Scholar · View at Scopus
  83. C. L. Sentman, J. R. Shutter, D. Hockenbery, O. Kanagawa, and S. J. Korsmeyer, “bcl-2 inhibits multiple forms of apoptosis but not negative selection in thymocytes,” Cell, vol. 67, no. 5, pp. 879–888, 1991. View at Google Scholar · View at Scopus
  84. D. Lee-Liu, G. Edwards-Faret, V. S. Tapia, and J. Larraín, “Spinal cord regeneration: Lessons for mammals from non-mammalian vertebrates,” Genesis, vol. 51, no. 8, pp. 529–544, 2013. View at Publisher · View at Google Scholar · View at Scopus
  85. T. M. Pirttimaki, S. D. Hall, and H. R. Parri, “Sustained neuronal activity generated by glial plasticity,” Journal of Neuroscience, vol. 31, no. 21, pp. 7637–7647, 2011. View at Publisher · View at Google Scholar · View at Scopus
  86. J. Wlodarczyk, I. Mukhina, L. Kaczmarek, and A. Dityatev, “Extracellular matrix molecules, their receptors, and secreted proteases in synaptic plasticity,” Developmental Neurobiology, vol. 71, no. 11, pp. 1040–1053, 2011. View at Publisher · View at Google Scholar · View at Scopus
  87. Y. Sugita, S. P. Becerra, G. J. Chader, and J. P. Schwartz, “Pigment epithelium-derived factor (PEDF) has direct effects on the metabolism and proliferation of microglia and indirect effects on astrocytes,” Journal of Neuroscience Research, vol. 49, pp. 710–718, 1997. View at Google Scholar
  88. V. Stellmach, S. E. Crawford, W. Zhou, and N. Bouck, “Prevention of ischemia-induced retinopathy by the natural ocular antiangiogenic agent pigment epithelium-derived factor,” Proceedings of the National Academy of Sciences of the United States of America, vol. 98, no. 5, pp. 2593–2597, 2001. View at Publisher · View at Google Scholar · View at Scopus
  89. D. N. Loy, C. H. Crawford, J. B. Darnall, D. A. Burke, S. M. Onifer, and S. R. Whittemore, “Temporal progression of angiogenesis and basal lamina deposition after contusive spinal cord injury in the adult rat,” Journal of Comparative Neurology, vol. 445, no. 4, pp. 308–324, 2002. View at Publisher · View at Google Scholar · View at Scopus
  90. G. Ferrari, A. R. Hajrasouliha, Z. Sadrai, H. Ueno, S. K. Chauhan, and R. Dana, “Nerves and neovessels inhibit each other in the cornea,” Investigative Ophthalmology and Visual Science, vol. 54, no. 1, pp. 813–820, 2013. View at Publisher · View at Google Scholar · View at Scopus
  91. M. L. Lemons, D. R. Howland, and D. K. Anderson, “Chondroitin sulfate proteoglycan immunoreactivity increases following spinal cord injury and transplantation,” Experimental Neurology, vol. 160, no. 1, pp. 51–65, 1999. View at Publisher · View at Google Scholar · View at Scopus
  92. W. B. J. Cafferty, P. Duffy, E. Huebner, and S. M. Strittmatter, “MAG and OMgp synergize with Nogo-A to restrict axonal growth and neurological recovery after spinal cord trauma,” Journal of Neuroscience, vol. 30, no. 20, pp. 6825–6837, 2010. View at Publisher · View at Google Scholar · View at Scopus
  93. W. B. J. Cafferty, S. Yang, P. J. Duffy, S. Li, and S. M. Strittmatter, “Functional axonal regeneration through astrocytic scar genetically modified to digest chondroitin sulfate proteoglycans,” Journal of Neuroscience, vol. 27, no. 9, pp. 2176–2185, 2007. View at Publisher · View at Google Scholar · View at Scopus
  94. K. Bartus, N. D. James, K. D. Bosch, and E. J. Bradbury, “Chondroitin sulphate proteoglycans: key modulators of spinal cord and brain plasticity,” Experimental Neurology, vol. 235, no. 1, pp. 5–17, 2012. View at Publisher · View at Google Scholar · View at Scopus
  95. J. R. Siebert and D. J. Osterhout, “The inhibitory effects of chondroitin sulfate proteoglycans on oligodendrocytes,” Journal of Neurochemistry, vol. 119, no. 1, pp. 176–188, 2011. View at Publisher · View at Google Scholar · View at Scopus
  96. B. I. Awad, M. A. Carmody, and M. P. Steinmetz, “Potential role of growth factors in the management of spinal cord injury,” World Neurosurgery, 2013. View at Publisher · View at Google Scholar
  97. H. Cheng, J. P. Wu, and S. F. Tzeng, “Neuroprotection of glial cell line-derived neurotrophic factor in damaged spinal cords following contusive injury,” Journal of Neuroscience Research, vol. 69, no. 3, pp. 397–405, 2002. View at Publisher · View at Google Scholar · View at Scopus
  98. S. Halegoua, R. C. Armstrong, and N. E. Kremer, “Dissecting the mode of action of a neuronal growth factor,” Current Topics in Microbiology and Immunology, vol. 165, pp. 119–169, 1991. View at Google Scholar · View at Scopus
  99. Y. Liu, B. T. Himes, M. Murray, A. Tessler, and I. Fischer, “Grafts of BDNF-producing fibroblasts rescue axotomized rubrospinal neurons and prevent their atrophy,” Experimental Neurology, vol. 178, no. 2, pp. 150–164, 2002. View at Publisher · View at Google Scholar · View at Scopus
  100. F. Gómez-Pinilla, Z. Ying, R. R. Roy, J. Hodgson, and V. R. Edgerton, “Afferent input modulates neurotrophins and synaptic plasticity in the spinal cord,” Journal of Neurophysiology, vol. 92, no. 6, pp. 3423–3432, 2004. View at Publisher · View at Google Scholar · View at Scopus
  101. K. Kasahara, T. Nakagawa, and T. Kubota, “Neuronal loss and expression of neurotrophic factors in a model of rat chronic compressive spinal cord injury,” Spine, vol. 31, no. 18, pp. 2059–2066, 2006. View at Publisher · View at Google Scholar · View at Scopus
  102. R. Grill, K. Murai, A. Blesch, F. H. Gage, and M. H. Tuszynski, “Cellular delivery of neurotrophin-3 promotes corticospinal axonal growth and partial functional recovery after spinal cord injury,” Journal of Neuroscience, vol. 17, no. 14, pp. 5560–5572, 1997. View at Google Scholar · View at Scopus
  103. M. H. Tuszynski, R. Grill, L. L. Jones et al., “NT-3 gene delivery elicits growth of chronically injured corticospinal axons and modestly improves functional deficits after chronic scar resection,” Experimental Neurology, vol. 181, no. 1, pp. 47–56, 2003. View at Publisher · View at Google Scholar · View at Scopus
  104. C. Iannotti, H. Li, P. Yan, X. Lu, L. Wirthlin, and X. Xu, “Glial cell line-derived neurotrophic factor-enriched bridging transplants promote propriospinal axonal regeneration and enhance myelination after spinal cord injury,” Experimental Neurology, vol. 183, no. 2, pp. 379–393, 2003. View at Publisher · View at Google Scholar · View at Scopus
  105. I. Mocchetti, S. J. Rabin, A. M. Colangelo, S. R. Whittemore, and J. R. Wrathall, “Increased basic fibroblast growth factor expression following contusive spinal cord injury,” Experimental Neurology, vol. 141, no. 1, pp. 154–164, 1996. View at Publisher · View at Google Scholar · View at Scopus
  106. R. Klein, “Eph/ephrin signaling in morphogenesis, neural development and plasticity,” Current Opinion in Cell Biology, vol. 16, no. 5, pp. 580–589, 2004. View at Publisher · View at Google Scholar · View at Scopus
  107. M. Hruska and M. B. Dalva, “Ephrin regulation of synapse formation, function and plasticity,” Molecular and Cellular Neuroscience, vol. 50, no. 1, pp. 35–44, 2012. View at Publisher · View at Google Scholar · View at Scopus
  108. R. Klein, “Bidirectional modulation of synaptic functions by Eph/ephrin signaling,” Nature Neuroscience, vol. 12, no. 1, pp. 15–20, 2009. View at Publisher · View at Google Scholar · View at Scopus
  109. Y. Goldshmit, M. D. Spanevello, S. Tajouri et al., “EphA4 blockers promote axonal regeneration and functional recovery following spinal cord injury in mice,” PLoS ONE, vol. 6, no. 9, Article ID e24636, 2011. View at Publisher · View at Google Scholar · View at Scopus
  110. A. Filosa, S. Paixo, S. D. Honsek et al., “Neuron-glia communication via EphA4/ephrin-A3 modulates LTP through glial glutamate transport,” Nature Neuroscience, vol. 12, no. 10, pp. 1285–1292, 2009. View at Publisher · View at Google Scholar · View at Scopus
  111. K. K. Murai and E. B. Pasquale, “Eph receptors and ephrins in neuron-astrocyte communication at synapses,” GLIA, vol. 59, no. 11, pp. 1567–1578, 2011. View at Publisher · View at Google Scholar · View at Scopus
  112. Y. Goldshmit, S. McLenachan, and A. Turnley, “Roles of Eph receptors and ephrins in the normal and damaged adult CNS,” Brain Research Reviews, vol. 52, no. 2, pp. 327–345, 2006. View at Publisher · View at Google Scholar · View at Scopus
  113. Y. Goldshmit, M. P. Galea, G. Wise, P. F. Bartlett, and A. M. Turnley, “Axonal regeneration and lack of astrocytic gliosis in EphA4-deficient mice,” The Journal of Neuroscience, vol. 24, no. 45, pp. 10064–10073, 2004. View at Publisher · View at Google Scholar · View at Scopus
  114. M. Irizarry-Ramírez, C. A. Willson, L. Cruz-Orengo et al., “Upregulation of EphA3 receptor after spinal cord injury,” Journal of Neurotrauma, vol. 22, no. 8, pp. 929–935, 2005. View at Publisher · View at Google Scholar · View at Scopus
  115. C. A. Willson, J. D. Miranda, R. D. Foster, S. M. Onifer, and S. R. Whittemore, “Transection of the adult rat spinal cord upregulates EphB3 receptor and ligand expression,” Cell Transplantation, vol. 12, no. 3, pp. 279–290, 2003. View at Google Scholar · View at Scopus
  116. J. Fabes, P. Anderson, C. Brennan, and S. Bolsover, “Regeneration-enhancing effects of EphA4 blocking peptide following corticospinal tract injury in adult rat spinal cord,” European Journal of Neuroscience, vol. 26, no. 9, pp. 2496–2505, 2007. View at Publisher · View at Google Scholar · View at Scopus
  117. Y. Goldshmit and J. Bourne, “Upregulation of epha4 on astrocytes potentially mediates astrocytic gliosis after cortical lesion in the marmoset monkey,” Journal of Neurotrauma, vol. 27, no. 7, pp. 1321–1332, 2010. View at Publisher · View at Google Scholar · View at Scopus
  118. X. Song, J. Zheng, J. Cao, W. Liu, and Z. Huang, “EphrinB-EphB receptor signaling contributes to neuropathic pain by regulating neural excitability and spinal synaptic plasticity in rats,” Pain, vol. 139, no. 1, pp. 168–180, 2008. View at Publisher · View at Google Scholar · View at Scopus
  119. A. A. Beg, J. E. Sommer, J. H. Martin, and P. Scheiffele, “α2-chimaerin is an essential EphA4 effector in the assembly of neuronal locomotor circuits,” Neuron, vol. 55, no. 5, pp. 768–778, 2007. View at Publisher · View at Google Scholar · View at Scopus
  120. O. Kiehn and S. J. B. Butt, “Physiological, anatomical and genetic identification of CPG neurons in the developing mammalian spinal cord,” Progress in Neurobiology, vol. 70, no. 4, pp. 347–361, 2003. View at Publisher · View at Google Scholar · View at Scopus
  121. K. Kullander, S. J. B. Butt, J. M. Lebret et al., “Role of EphA4 and EphrinB3 in local neuronal circuits that control walking,” Science, vol. 299, no. 5614, pp. 1889–1892, 2003. View at Publisher · View at Google Scholar · View at Scopus
  122. A. Vallstedt and K. Kullander, “Dorsally derived spinal interneurons in locomotor circuits,” Annals of the New York Academy of Sciences, vol. 1279, no. 1, pp. 32–42, 2013. View at Publisher · View at Google Scholar · View at Scopus
  123. Z. Zhuang, B. Yang, M. H. Theus et al., “EphrinBs regulate D-serine synthesis and release in astrocytes,” The Journal of Neuroscience, vol. 30, no. 47, pp. 16015–16024, 2010. View at Publisher · View at Google Scholar · View at Scopus
  124. C. G. Gerin, I. C. Madueke, T. Perkins et al., “Combination strategies for repair, plasticity, and regeneration using regulation of gene expression during the chronic phase after spinal cord injury,” Synapse, vol. 65, no. 12, pp. 1255–1281, 2011. View at Publisher · View at Google Scholar · View at Scopus
  125. K. Temporin, H. Tanaka, Y. Kuroda et al., “IL-1β promotes neurite outgrowth by deactivating RhoA via p38 MAPK pathway,” Biochemical and Biophysical Research Communications, vol. 365, no. 2, pp. 375–380, 2008. View at Publisher · View at Google Scholar · View at Scopus
  126. S. Conrad, H. J. Schluesener, K. Trautmann, N. Joannin, R. Meyermann, and J. M. Schwab, “Prolonged lesional expression of RhoA and RhoB following spinal cord injury,” Journal of Comparative Neurology, vol. 487, no. 2, pp. 166–175, 2005. View at Publisher · View at Google Scholar · View at Scopus
  127. M. K. Erschbamer, C. P. Hofstetter, and L. Olson, “RhoA, RhoB, RhoC, Rac1, Cdc42, and Tc10 mRNA levels in spinal cord, sensory ganglia, and corticospinal tract neurons and long-lasting specific changes following spinal cord injury,” Journal of Comparative Neurology, vol. 484, no. 2, pp. 224–233, 2005. View at Publisher · View at Google Scholar · View at Scopus
  128. J. Sung, L. Miao, J. W. Calvert, L. Huang, H. L. Harkey, and J. H. Zhang, “A possible role of RhoA/Rho-kinase in experimental spinal cord injury in rat,” Brain Research, vol. 959, no. 1, pp. 29–38, 2003. View at Publisher · View at Google Scholar · View at Scopus