Gene therapy, neurotrophic factors and spinal cord regeneration

Handbook of Clinical Neurology

Volumn 109, Issue , 2012, Pages 563-574

  Blesch, Armin ^a,c   Fischer, Itzhak ^b   Tuszynski, Mark H ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b DREXEL UNIVERSITY COLLEGE OF MEDICINE   (United States)

^c UNIVERSITY HOSPITAL HEIDELBERG   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 84867807061     PISSN: 00729752     EISSN: None     Source Type: Book Series    
DOI: 10.1016/B978-0-444-52137-8.00035-8     Document Type: Chapter

References (133)

1. Alto L.T., Havton L.A., Conner J.M., et al. Chemotropic guidance facilitates axonal regeneration and synapse formation after spinal cord injury. Nat Neurosci 2009, 12:1106-1113.
2. Ankeny D.P., McTigue D.M., Jakeman L.B. Bone marrow transplants provide tissue protection and directional guidance for axons after contusive spinal cord injury in rats. Exp Neurol 2004, 190:17-31.
3. Ballermann M., Fouad K. Spontaneous locomotor recovery in spinal cord injured rats is accompanied by anatomical plasticity of reticulospinal fibers. Eur J Neurosci 2006, 23:1988-1996.
4. Bamber N.I., Li H., Lu X., et al. Neurotrophins BDNF and NT-3 promote axonal re-entry into the distal host spinal cord through Schwann cell-seeded mini-channels. Eur J Neurosci 2001, 13:257-268.
5. Bareyre F.M., Kerschensteiner M., Raineteau O., et al. The injured spinal cord spontaneously forms a new intraspinal circuit in adult rats. Nat Neurosci 2004, 7:269-277.
6. Benson M.D., Romero M.I., Lush M.E., et al. Ephrin-B3 is a myelin-based inhibitor of neurite outgrowth. Proc Natl Acad Sci U S A 2005, 102:10694-10699.
7. Blesch A., Tuszynski M.H. Cellular GDNF delivery promotes growth of motor and dorsal column sensory axons after partial and complete spinal cord transection, and induces remyelination. J Comp Neurol 2003, 467:403-417.
8. Blesch A., Tuszynski M.H. Transient growth factor delivery sustains regenerated axons after spinal cord injury. J Neurosci 2007, 27:10535-10545.
9. Blesch A., Tuszynski M.H. Spinal cord injury: plasticity, regeneration and the challenge of translational drug development. Trends Neurosci 2009, 32:41-47.
10. Blesch A., Uy H.S., Grill R.J., et al. LIF augments corticospinal axon growth and neurotrophin expression after adult CNS injury. J Neurosci 1999, 19:3556-3566.
11. Blesch A., Yang H., Weidner N., et al. Axonal responses to cellularly delivered NT-4/5 after spinal cord injury. Mol Cell Neurosci 2004, 27:190-201.
12. Blesch A., Lu P., Roet K., et al. Phosphodiesterase-IV inhibitors and conditioning lesions in combination with lentiviral NT-3 gene transfer promote sensory axonal bridging across C3 spinal cord lesions. 2006 Abstract Viewer/Itinerary Planner 2006, Society for Neuroscience, Atlanta, GA, 2006. Online.: Program No. 522.10.
13. Blits B., Dijkhuizen P.A., Boer G.J., et al. Intercostal nerve implants transduced with an adenoviral vector encoding neurotrophin-3 promote regrowth of injured rat corticospinal tract fibers and improve hindlimb function. Exp Neurol 2000, 164:25-37.
14. Bolsover S., Fabes J., Anderson P.N. Axonal guidance molecules and the failure of axonal regeneration in the adult mammalian spinal cord. Restor Neurol Neurosci 2008, 26:117-130.
15. Bonner J.F., Blesch A., Neuhuber B., et al. Promoting directional axon growth from neural progenitors grafted into the injured spinal cord. J Neurosci Res 2010, 88:1182-1192.
16. Boyce V.S., Tumolo M., Fischer I., et al. Neurotrophic factors promote and enhance locomotor recovery in untrained spinalized cats. J Neurophysiol 2007, 98:1988-1996.
17. Bradbury E.J., Khemani S., Von R., et al. NT-3 promotes growth of lesioned adult rat sensory axons ascending in the dorsal columns of the spinal cord. Eur J Neurosci 1999, 11:3873-3883.
18. Bregman B.S., Kunkel-Bagden E., Reier P.J., et al. Recovery of function after spinal cord injury: mechanisms underlying transplant-mediated recovery of function differ after spinal cord injury in newborn and adult rats. Exp Neurol 1993, 123:3-16.
19. Cafferty W.B., Gardiner N.J., Das P., et al. Conditioning injury-induced spinal axon regeneration fails in interleukin-6 knock-out mice. J Neurosci 2004, 24:4432-4443.
20. Cai D., Qiu J., Cao Z., et al. Neuronal cyclic AMP controls the developmental loss in ability of axons to regenerate. J Neurosci 2001, 21:4731-4739.
21. Cao L., Liu L., Chen Z.Y., et al. Olfactory ensheathing cells genetically modified to secrete GDNF to promote spinal cord repair. Brain 2004, 127:535-549.
22. Cao Q., Xu X.M., Devries W.H., et al. Functional recovery in traumatic spinal cord injury after transplantation of multineurotrophin-expressing glial-restricted precursor cells. J Neurosci 2005, 25:6947-6957.
23. Cao Z., Gao Y., Bryson J.B., et al. The cytokine interleukin-6 is sufficient but not necessary to mimic the peripheral conditioning lesion effect on axonal growth. J Neurosci 2006, 26:5565-5573.
24. Chen Q., Zhou L., Shine H.D. Expression of neurotrophin-3 promotes axonal plasticity in the acute but not chronic injured spinal cord. J Neurotrauma 2006, 23:1254-1260.
25. Chen Q., Smith G.M., Shine H.D. Immune activation is required for NT-3-induced axonal plasticity in chronic spinal cord injury. Exp Neurol 2008, 209:497-509.
26. Costigan M., Befort K., Karchewski L., et al. Replicate high-density rat genome oligonucleotide microarrays reveal hundreds of regulated genes in the dorsal root ganglion after peripheral nerve injury. BMC Neurosci 2002, 3:16.
27. Courtine G., Song B., Roy R.R., et al. Recovery of supraspinal control of stepping via indirect propriospinal relay connections after spinal cord injury. Nat Med 2008, 14:69-74.
28. David S., Aguayo A.J. Axonal elongation into peripheral nervous system " bridges" after central nervous system injury in adult rats. Science 1981, 214:931-933.
29. de Leon R.D. Could neurotrophins replace treadmill training as locomotor therapy following spinal cord injury? Focus on " neurotrophic factors promote and enhance locomotor recovery in untrained spinalized cats" J Neurophysiol 2007, 98:1845-1846.
30. de Leon R.D., Acosta C.N. Effect of robotic-assisted treadmill training and chronic quipazine treatment on hindlimb stepping in spinally transected rats. J Neurotrauma 2006, 23:1147-1163.
31. Dhoot N.O., Tobias C.A., Fischer I., et al. Peptide-modified alginate surfaces as a growth permissive substrate for neurite outgrowth. J Biomed Mater Res A 2004, 71:191-200.
32. Dobkin B., Apple D., Barbeau H., et al. Weight-supported treadmill vs over-ground training for walking after acute incomplete SCI. Neurology 2006, 66:484-493.
33. Edgerton V.R., Leon R.D., Harkema S.J., et al. Retraining the injured spinal cord. J Physiol 2001, 533:15-22.
34. Fawcett J.W., Curt A., Steeves J.D., et al. Guidelines for the conduct of clinical trials for spinal cord injury as developed by the ICCP panel: spontaneous recovery after spinal cord injury and statistical power needed for therapeutic clinical trials. Spinal Cord 2007, 45:190-205.
35. Fernandes K.J., Fan D.P., Tsui B.J., et al. Influence of the axotomy to cell body distance in rat rubrospinal and spinal motoneurons: differential regulation of GAP-43, tubulins, and neurofilament-M. J Comp Neurol 1999, 414:495-510.
36. Filbin M.T. Myelin-associated inhibitors of axonal regeneration in the adult mammalian CNS. Nat Rev Neurosci 2003, 4:703-713.
37. Fitch M.T., Silver J. CNS injury, glial scars, and inflammation: Inhibitory extracellular matrices and regeneration failure. Exp Neurol 2008, 209:294-301.
38. Gao Y., Nikulina E., Mellado W., et al. Neurotrophins elevate cAMP to reach a threshold required to overcome inhibition by MAG through extracellular signal-regulated kinase-dependent inhibition of phosphodiesterase. J Neurosci 2003, 23:11770-11777.
39. Gao Y., Deng K., Hou J., et al. Activated CREB is sufficient to overcome inhibitors in myelin and promote spinal axon regeneration in vivo. Neuron 2004, 44:609-621.
40. Giehl K.M., Tetzlaff W. BDNF and NT-3, but not NGF, prevent axotomy-induced death of rat corticospinal neurons in vivo. Eur J Neurosci 1996, 8:1167-1175.
41. Gomez-Pinilla F., Ying Z., Opazo P., et al. Differential regulation by exercise of BDNF and NT-3 in rat spinal cord and skeletal muscle. Eur J Neurosci 2001, 13:1078-1084.
42. Grill R., Murai K., Blesch A., et al. Cellular delivery of neurotrophin-3 promotes corticospinal axonal growth and partial functional recovery after spinal cord injury. J Neurosci 1997, 17:5560-5572.
43. Grill R.J., Blesch A., Tuszynski M.H. Robust growth of chronically injured spinal cord axons induced by grafts of genetically modified NGF-secreting cells. Exp Neurol 1997, 148:444-452.
44. Hiebert G.W., Khodarahmi K., McGraw J., et al. Brain-derived neurotrophic factor applied to the motor cortex promotes sprouting of corticospinal fibers but not regeneration into a peripheral nerve transplant. J Neurosci Res 2002, 69:160-168.
45. Himes B.T., Liu Y., Solowska J.M., et al. Transplants of cells genetically modified to express neurotrophin-3 rescue axotomized Clarke's nucleus neurons after spinal cord hemisection in adult rats. J Neurosci Res 2001, 65:549-564.
46. Hofstetter C.P., Schwarz E.J., Hess D., et al. Marrow stromal cells form guiding strands in the injured spinal cord and promote recovery. Proc Natl Acad Sci U S A 2002, 99:2199-2204.
47. Hollis E.R., Lu P., Blesch A., et al. IGF-I gene delivery promotes corticospinal neuronal survival but not regeneration after adult CNS injury. Exp Neurol 2009, 215:53-59.
48. Houle J.D., Tessler A. Repair of chronic spinal cord injury. Exp Neurol 2003, 182:247-260.
49. Houle J.D., Ye J.H. Survival of chronically-injured neurons can be prolonged by treatment with neurotrophic factors. Neurosci 1999, 94:929-936.
50. Jakeman L.B., Wei P., Guan Z., et al. Brain-derived neurotrophic factor stimulates hindlimb stepping and sprouting of cholinergic fibers after spinal cord injury. Exp Neurol 1998, 154:170-184.
51. Jin Y., Tessler A., Fischer I., et al. Fibroblasts genetically modified to produce BDNF support regrowth of chronically injured serotonergic axons. Neurorehabil Neural Repair 2000, 14:311-317.
52. Jin Y., Fischer I., Tessler A., et al. 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.
53. Jin Y., Ziemba K.S., Smith G.M. Axon growth across a lesion site along a preformed guidance pathway in the brain. Exp Neurol 2008, 210:521-530.
54. Jones L.L., Tuszynski M.H. Spinal cord injury elicits expression of keratan sulfate proteoglycans by macrophages, reactive microglia, and oligodendrocyte progenitors. J Neurosci 2002, 22:4611-4624.
55. Jones L.L., Sajed D., Tuszynski M.H. Axonal regeneration through regions of chondroitin sulfate proteoglycan deposition after spinal cord injury: a balance of permissiveness and inhibition. J Neurosci 2003, 23:9276-9288.
56. Kadoya K., Tsukada S., Lu P., et al. Combined intrinsic and extrinsic neuronal mechanisms facilitate bridging axonal regeneration one year after spinal cord injury. Neuron 2009, 64:165-172.
57. Kobayashi N.R., Fan D.P., Giehl K.M., et al. BDNF and NT-4/5 prevent atrophy of rat rubrospinal neurons after cervical axotomy, stimulate GAP-43 and Talpha1-tubulin mRNA expression, and promote axonal regeneration. J Neurosci 1997, 17:9583-9595.
58. Kwon B.K., Liu J., Messerer C., et al. Survival and regeneration of rubrospinal neurons 1 year after spinal cord injury. Proc Natl Acad Sci U S A 2002, 99:3246-3251.
59. Kwon B.K., Liu J., Lam C., et al. Brain-derived neurotrophic factor gene transfer with adeno-associated viral and lentiviral vectors prevents rubrospinal neuronal atrophy and stimulates regeneration-associated gene expression after acute cervical spinal cord injury. Spine 2007, 32:1164-1173.
60. Leblond H., L'Esperance M., Orsal D., et al. Treadmill locomotion in the intact and spinal mouse. J Neurosci 2003, 23:11411-11419.
61. Lepore A.C., Fischer I. Lineage-restricted neural precursors survive, migrate, and differentiate following transplantation into the injured adult spinal cord. Exp Neurol 2005, 194:230-242.
62. Levi-Montalcini R., Hamburger V. Selective growth stimulating effects of mouse sarcoma on the sensory and sympathetic nervous system of the chick embryo. J Exp Zool 1951, 116:321-361.
63. Li Y., Raisman G. Schwann cells induce sprouting in motor and sensory axons in the adult rat spinal cord. J Neurosci 1994, 14:4050-4063.
64. Li Y., Field M., Raisman G. Repair of adult rat corticospinal tract by transplants of olfactory ensheathing cells. Science 1997, 277:2000-2002.
65. Liu Y., Himes B.T., Solowska J., et al. Intraspinal delivery of neurotrophin-3 using neural stem cells genetically modified by recombinant retrovirus. Exp Neurol 1999, 158:9-26.
66. Liu Y., Kim D., Himes B.T., et al. Transplants of fibroblasts genetically modified to express brain-derived neurotrophic factor promote regeneration of adult rat rubrospinal axons and recovery of forelimb function. J Neurosci 1999, 19:4370-4387.
67. Lovely R.G., Gregor R.J., Roy R.R., et al. Effects of training on the recovery of full-weight-bearing stepping in the adult spinal cat. Exp Neurol 1986, 92:421-435.
68. Low K., Culbertson M., Bradke F., et al. Netrin-1 is a novel myelin-associated inhibitor to axon growth. J Neurosci 2008, 28:1099-1108.
69. Lu P., Blesch A., Tuszynski M.H. Neurotrophism without neurotropism: BDNF promotes survival but not growth of lesioned corticospinal neurons. J Comp Neurol 2001, 436:456-470.
70. Lu P., Jones L.L., Snyder E.Y., et al. Neural stem cells constitutively secrete neurotrophic factors and promote extensive host axonal growth after spinal cord injury. Exp Neurol 2003, 181:115-129.
71. Lu P., Yang H., Jones L.L., et al. Combinatorial therapy with neurotrophins and cAMP promotes axonal regeneration beyond sites of spinal cord injury. J Neurosci 2004, 24:6402-6409.
72. Lu P., Jones L.L., Tuszynski M.H. BDNF-expressing marrow stromal cells support extensive axonal growth at sites of spinal cord injury. Exp Neurol 2005, 191:344-360.
73. Lu P., Yang H., Culbertson M., et al. Olfactory ensheathing cells do not exhibit unique migratory or axonal growth-promoting properties after spinal cord injury. J Neurosci 2006, 26:11120-11130.
74. Lu P., Jones L.L., Tuszynski M.H. Axon regeneration through scars and into sites of chronic spinal cord injury. Exp Neurol 2007, 203:8-21.
75. Massey J.M., Hubscher C.H., Wagoner M.R., 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.
76. Massey J.M., Amps J., Viapiano M.S., et al. Increased chondroitin sulfate proteoglycan expression in denervated brainstem targets following spinal cord injury creates a barrier to axonal regeneration overcome by chondroitinase ABC and neurotrophin-3. Exp Neurol 2008, 209:426-445.
77. McTigue D.M., Horner P.J., Stokes B.T., et al. Neurotrophin-3 and brain-derived neurotrophic factor induce oligodendrocyte proliferation and myelination of regenerating axons in the contused adult rat spinal cord. J Neurosci 1998, 18:5354-5365.
78. Menei P., Montero-Menei C., Whittemore S.R., et al. Schwann cells genetically modified to secrete human BDNF promote enhanced axonal regrowth across transected adult rat spinal cord. Eur J Neurosci 1998, 10:607-621.
79. Mitsui T., Fischer I., Shumsky J.S., et al. Transplants of fibroblasts expressing BDNF and NT-3 promote recovery of bladder and hindlimb function following spinal contusion injury in rats. Exp Neurol 2005, 194:410-431.
80. Mori F., Himes B.T., Kowada M., et al. Fetal spinal cord transplants rescue some axotomized rubrospinal neurons from retrograde cell death in adult rats. Exp Neurol 1997, 143:45-60.
81. Murray M., Goldberger M.E. Restitution of function and collateral sprouting in the cat spinal cord: the partially hemisected animal. J Comp Neurol 1974, 158:19-36.
82. Neumann S., Woolf C.J. Regeneration of dorsal column fibers into and beyond the lesion site following adult spinal cord injury. Neuron 1999, 23:83-91.
83. Neumann S., Bradke F., Tessier-Lavigne M., et al. Regeneration of sensory axons within the injured spinal cord induced by intraganglionic cAMP elevation. Neuron 2002, 34:885-893.
84. Niclou S.P., Franssen E.H., Ehlert E.M., et al. Meningeal cell-derived semaphorin 3A inhibits neurite outgrowth. Mol Cell Neurosci 2003, 24:902-912.
85. Nikulina E., Tidwell J.L., Dai H.N., et al. The phosphodiesterase inhibitor rolipram delivered after a spinal cord lesion promotes axonal regeneration and functional recovery. Proc Natl Acad Sci U S A 2004, 101:8786-8790.
86. Ozdinler P.H., Macklis J.D. IGF-I specifically enhances axon outgrowth of corticospinal motor neurons. Nat Neurosci 2006, 9:1371-1381.
87. Park K.I., Himes B.T., Stieg P.E., et al. Neural stem cells may be uniquely suited for combined gene therapy and cell replacement: Evidence from engraftment of Neurotrophin-3-expressing stem cells in hypoxic-ischemic brain injury. Exp Neurol 2006, 199:179-190.
88. Park K.K., Liu K., Hu Y., et al. Promoting axon regeneration in the adult CNS by modulation of the PTEN/mTOR pathway. Science 2008, 322:963-966.
89. Pearse D.D., Pereira F.C., Marcillo A.E., et al. cAMP and Schwann cells promote axonal growth and functional recovery after spinal cord injury. Nat Med 2004, 10:610-616.
90. Pfeifer K., Vroemen M., Blesch A., et al. Adult neural progenitor cells provide a permissive guiding substrate for corticospinal axon growth following spinal cord injury. Eur J Neurosci 2004, 20:1695-1704.
91. Qiu J., Cai D., Dai H., et al. Spinal axon regeneration induced by elevation of cyclic AMP. Neuron 2002, 34:895-903.
92. Qiu J., Cafferty W.B., McMahon S.B., et al. Conditioning injury-induced spinal axon regeneration requires signal transducer and activator of transcription 3 activation. J Neurosci 2005, 25:1645-1653.
93. Ramón-Cueto A., Nieto-Sampedro M. Regeneration into the spinal cord of transected dorsal root axons is promoted by ensheathing glia transplants. Exp Neurol 1994, 127:232-244.
94. Richardson P.M., Issa V.M. Peripheral injury enhances central regeneration of primary sensory neurones. Nature 1984, 309:791-793.
95. Richardson P.M., McGuinness U.M., Aguayo A.J. Axons from CNS neurons regenerate into PNS grafts. Nature 1980, 284:264-265.
96. Richter M.W., Roskams A.J. Olfactory ensheathing cell transplantation following spinal cord injury: hype or hope?. Exp Neurol 2008, 209:353-367.
97. Ruitenberg M.J., Plant G.W., Hamers F.P., et al. Ex vivo adenoviral vector-mediated neurotrophin gene transfer to olfactory ensheathing glia: effects on rubrospinal tract regeneration, lesion size, and functional recovery after implantation in the injured rat spinal cord. J Neurosci 2003, 23:7045-7058.
98. Ruitenberg M.J., Blits B., Dijkhuizen P.A., et al. Adeno-associated viral vector-mediated gene transfer of brain-derived neurotrophic factor reverses atrophy of rubrospinal neurons following both acute and chronic spinal cord injury. Neurobiol Dis 2004, 15:394-406.
99. Ruitenberg M.J., Levison D.B., Lee S.V., et al. NT-3 expression from engineered olfactory ensheathing glia promotes spinal sparing and regeneration. Brain 2005, 128:839-853.
100. Schnell L., Schneider R., Kolbeck R., et al. Neurotrophin-3 enhances sprouting of corticospinal tract during development and after adult spinal cord lesion. Nature 1994, 367:170-173.
101. Schuman E.M. Neurotrophin regulation of synaptic transmission. Curr Opin Neurobiol 1999, 9:105-109.
102. Seijffers R., Allchorne A.J., Woolf C.J. The transcription factor ATF-3 promotes neurite outgrowth. Mol Cell Neurosci 2006, 32:143-154.
103. Seijffers R., Mills C.D., Woolf C.J. ATF3 increases the intrinsic growth state of DRG neurons to enhance peripheral nerve regeneration. J Neurosci 2007, 27:7911-7920.
104. Silver J., Miller J.H. Regeneration beyond the glial scar. Nat Rev Neurosci 2004, 5:146-156.
105. Stam F.J., MacGillavry H.D., Armstrong N.J., et al. Identification of candidate transcriptional modulators involved in successful regeneration after nerve injury. Eur J Neurosci 2007, 25:3629-3637.
106. Stokes B.T., Reier P.J. Fetal grafts alter chronic behavioral outcome after contusion damage to the adult rat spinal cord. Exp Neurol 1992, 116:1-12.
107. Taylor L., Jones L., Tuszynski M.H., et al. Neurotrophin-3 gradients established by lentiviral gene delivery promote short-distance axonal bridging beyond cellular grafts in the injured spinal cord. J Neurosci 2006, 26:9713-9721.
108. Tessler A. Intraspinal transplants. Ann Neurol 1991, 29:115-123.
109. Tessler A., Fischer I., Giszter S., et al. Embryonic spinal cord transplants enhance locomotor performance in spinalized newborn rats. Adv Neurol 1997, 72:291-303.
110. Tobias C.A., Dhoot N.O., Wheatley M.A., et al. Grafting of encapsulated BDNF-producing fibroblasts into the injured spinal cord without immune suppression in adult rats. J Neurotrauma 2001, 18:287-301.
111. Tobias C.A., Shumsky J.S., Shibata M., 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.
112. Tobias C.A., Han S.S., Shumsky J.S., et al. Alginate encapsulated BDNF-producing fibroblast grafts permit recovery of function after spinal cord injury in the absence of immune suppression. J Neurotrauma 2005, 22:138-156.
113. Tuszynski M.H., Peterson D.A., Ray J., et al. Fibroblasts genetically modified to produce nerve growth factor induce robust neuritic ingrowth after grafting to the spinal cord. Exp Neurol 1994, 126:1-14.
114. Tuszynski M.H., Gabriel K., Gage F.H., et al. Nerve growth factor delivery by gene transfer induces differential outgrowth of sensory, motor, and noradrenergic neurites after adult spinal cord injury. Exp Neurol 1996, 137:157-173.
115. Tuszynski M.H., Weidner N., McCormack M., et al. Grafts of genetically modified Schwann cells to the spinal cord: survival, axon growth, and myelination. Cell Transplant 1998, 7:187-196.
116. Tuszynski M.H., Grill R., Jones L.L., et al. NT-3 gene delivery elicits growth of chronically injured corticospinal axons and modestly improves functional deficits after chronic scar resection. Exp Neurol 2003, 181:47-56.
117. Wannier T., Schmidlin E., Bloch J., et al. A unilateral section of the corticospinal tract at cervical level in primate does not lead to measurable cell loss in motor cortex. J Neurotrauma 2005, 22:703-717.
118. Weidner N., Blesch A., Grill R.J., et al. Nerve growth factor-hypersecreting Schwann cell grafts augment and guide spinal cord axonal growth and remyelinate central nervous systen axons in a phenotypically appropriate manner that correlates with expression of L1. J Comp Neurol 1999, 413:495-506.
119. Weidner N., Ner A., Salimi N., et al. Spontaneous corticospinal axonal plasticity and functional recovery after adult central nervous system injury. Proc Natl Acad Sci U S A 2001, 98:3513-3518.
120. Wong L.F., Yip P.K., Battaglia A., et al. Retinoic acid receptor beta2 promotes functional regeneration of sensory axons in the spinal cord. Nat Neurosci 2006, 9:243-250.
121. Wu D., Zhang Y., Bo X., et al. Actions of neuropoietic cytokines and cyclic AMP in regenerative conditioning of rat primary sensory neurons. Exp Neurol 2006, 204:66-76.
122. Xiao H.S., Huang Q.H., Zhang F.X., et al. Identification of gene expression profile of dorsal root ganglion in the rat peripheral axotomy model of neuropathic pain. Proc Natl Acad Sci U S A 2002, 99:8360-8365.
123. Xie F., Zheng B. White matter inhibitors in CNS axon regeneration failure. Exp Neurol 2008, 209:302-312.
124. Xu X.M., Guenard V., Kleitman N., et al. Axonal regeneration into Schwann cell-seeded guidance channels grafted into transected adult rat spinal cord. J Comp Neurol 1994, 351:145-160.
125. Xu X.M., Guenard V., Kleitman N., et al. A combination of BDNF and NT-3 promotes supraspinal axonal regeneration into Schwann cell grafts in adult rat thoracic spinal cord. Exp Neurol 1995, 134:261-272.
126. Xu X.M., Chen A., Guenard V., et al. Bridging Schwann cell transplants promote axonal regeneration from both the rostral and caudal stumps of transected adult rat spinal cord. J Neurocytol 1997, 26:1-16.
127. Yakovenko S., Kowalczewski J., Prochazka A. Intraspinal stimulation caudal to spinal cord transections in rats. Testing the propriospinal hypothesis. J Neurophysiol 2007, 97:2570-2574.
128. Ye J.H., Houle J.D. Treatment of the chronically injured spinal cord with neurotrophic factors can promote axonal regeneration from supraspinal neurons. Exp Neurol 1997, 143:70-81.
129. Ying Z., Roy R.R., Edgerton V.R., et al. Exercise restores levels of neurotrophins and synaptic plasticity following spinal cord injury. Exp Neurol 2005, 193:411-419.
130. Zhang Y., Dijkhuizen P.A., Anderson P.N., et al. NT-3 delivered by an adenoviral vector induces injured dorsal root axons to regenerate into the spinal cord of adult rats. J Neurosci Res 1998, 54:554-562.
131. Zhang Y., Zhang X., Wu D., et al. Lentiviral-mediated expression of polysialic acid in spinal cord and conditioning lesion promote regeneration of sensory axons into spinal cord. Mol Ther 2007, 15:1796-1804.
132. Zhou L., Baumgartner B.J., Hill-Felberg S.J., et al. Neurotrophin-3 expressed in situ induces axonal plasticity in the adult injured spinal cord. J Neurosci 2003, 23:1424-1431.
133. Ziemba K.S., Chaudhry N., Rabchevsky A.G., et al. Targeting axon growth from neuronal transplants along preformed guidance pathways in the adult CNS. J Neurosci 2008, 28:340-348.