Pathogenesis and molecular targeted therapy of spinal and bulbar muscular atrophy (SBMA)

Cell and Tissue Research

Volumn 349, Issue 1, 2012, Pages 313-320

  Banno, Haruhiko ^a,b   Katsuno, Masahisa ^a   Suzuki, Keisuke ^a   Tanaka, Fumiaki ^a   Sobue, Gen ^a  

^a NAGOYA UNIVERSITY GRADUATE SCHOOL OF MEDICINE   (Japan)

^b NAGOYA UNIVERSITY   (Japan)

Author keywords

Androgen receptor (AR); Clinical trial; Leuprorelin; Polyglutamine disease; Spinal and bulbar muscular atrophy (SBMA)

Indexed keywords

5 HYDROXY 1,7 BIS(3,4 DIMETHOXYPHENYL) 1,4,6 HEPTATRIEN 3 ONE; ALVESPIMYCIN; ANDROGEN RECEPTOR; ASC J 9; BUTYRIC ACID; CURCUMIN; DUTASTERIDE; LEUPRORELIN; PLACEBO; TANESPIMYCIN; UNCLASSIFIED DRUG;

CELL NUCLEUS INCLUSION BODY; DISORDERS OF MITOCHONDRIAL FUNCTIONS; DRUG EFFECT; DRUG MECHANISM; DRUG TARGETING; DRUG TOLERABILITY; HISTOPATHOLOGY; HUMAN; KENNEDY DISEASE; MITOCHONDRIAL DYSFUNCTIONS; MOLECULAR DYNAMICS; MOLECULAR PATHOLOGY; MOLECULARLY TARGETED THERAPY; NERVE FIBER TRANSPORT; NEUROPATHOLOGY; NONHUMAN; OXIDATIVE STRESS; PRIORITY JOURNAL; PROTEIN DNA BINDING; REVIEW; TRANSCRIPTION REGULATION; TRANSCRIPTIONAL DYSREGULATION;

ANIMALS; BULBO-SPINAL ATROPHY, X-LINKED; CLINICAL TRIALS AS TOPIC; HUMANS; LEUPROLIDE; MOLECULAR TARGETED THERAPY;

ANIMALIA;

EID: 84862764590     PISSN: 0302766X     EISSN: 14320878     Source Type: Journal    
DOI: 10.1007/s00441-012-1377-9     Document Type: Review

References (150)

1. Alilain WJ, Horn KP, Hu H, Dick TE, Silver J (2011) Functional regeneration of respiratory pathways after spinal cord injury. Nature 475:196-200
2. Alto LT, Havton LA, Conner JM, Hollis Ii ER, Blesch A, Tuszynski MH (2009) Chemotropic guidance facilitates axonal regeneration and synapse formation after spinal cord injury. Nat Neurosci 12:1106-1113
3. Andrews MR, Czvitkovich S, Dassie E, Vogelaar CF, Faissner A, Blits B, Gage FH, ffrench-Constant C, Fawcett JW (2009) Alpha9 integrin promotes neurite outgrowth on tenascin-C and enhances sensory axon regeneration. J Neurosci 29:5546-5557
4. Ankeny DP, McTigue DM, Jakeman LB (2004) Bone marrow transplants provide tissue protection and directional guidance for axons after contusive spinal cord injury in rats. Exp Neurol 190:17-31 (Pubitemid 39335703)
5. Ballermann M, Fouad K (2006) Spontaneous locomotor recovery in spinal cord injured rats is accompanied by anatomical plasticity of reticulospinal fibers. Eur J Neurosci 23:1988-1996
6. Bareyre FM, Kerschensteiner M, Raineteau O, Mettenleiter TC, Weinmann O, Schwab ME (2004) The injured spinal cord spontaneously forms a new intraspinal circuit in adult rats. Nat Neurosci 7:269-277 (Pubitemid 38280451)
7. Barritt AW, Davies M, Marchand F, Hartley R, Grist J, Yip P, McMahon SB, Bradbury EJ (2006) Chondroitinase ABC promotes sprouting of intact and injured spinal systems after spinal cord injury. J Neurosci 26:10856-10867
8. Bartus K, James ND, Bosch KD, Bradbury EJ (2011) Chondroitin sulphate proteoglycans: key modulators of spinal cord and brain plasticity. Exp Neurol. doi:10.1016/j.expneurol.2011.08.008
9. Bethea JR, Dietrich WD (2002) Targeting the host inflammatory response in traumatic spinal cord injury. Curr Opin Neurol 15:355-360
10. Blackmore MG, Moore DL, Smith RP, Goldberg JL, Bixby JL, Lemmon VP (2010) High content screening of cortical neurons identifies novel regulators of axon growth. Mol Cell Neurosci 44:43-54
11. Blesch A, Tuszynski MH (2003) 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 467:403-417 (Pubitemid 37421083)
12. Blesch A, Tuszynski MH (2007) Transient growth factor delivery sustains regenerated axons after spinal cord injury. J Neurosci 27:10535-10545 (Pubitemid 47501998)
13. Blesch A, Yang H, Weidner N, Hoang A, Otero D (2004) Axonal responses to cellularly delivered NT-4/5 after spinal cord injury. Mol Cell Neurosci 27:190-201 (Pubitemid 39370100)
14. Blesch A, Lu P, Tsukada S, Taylor L, Roet K, Coppola G, Geschwind D, Tuszynski MH (2011) Conditioning lesions before or after spinal cord injury recruit broad genetic mechanisms that sustain axonal regeneration: superiority to cAMP-mediated effects. Exp Neurol. doi:10.1016/j.expneurol.2011.12.037
15. Blits B, Dijkhuizen PA, Boer GJ, Verhaagen J (2000) 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 164:25-37
16. Bonner JF, Blesch A, Neuhuber B, Fischer I (2010) Promoting directional axon growth from neural progenitors grafted into the injured spinal cord. J Neurosci Res 88:1182-1192
17. Bonner JF, Connors TM, Silverman WF, Kowalski DP, Lemay MA, Fischer I (2011) Grafted neural progenitors integrate and restore synaptic connectivity across the injured spinal cord. J Neurosci 31:4675-4686
18. Boyd JG, Gordon T (2003) Neurotrophic factors and their receptors in axonal regeneration and functional recovery after peripheral nerve injury. Mol Neurobiol 27:277-324
19. Bradbury EJ, Khemani S, Von R, King PJV, McMahon SB (1999) NT- 3 promotes growth of lesioned adult rat sensory axons ascending in the dorsal columns of the spinal cord. Eur J Neurosci 11:3873-3883 (Pubitemid 29537567)
20. Bradbury EJ, Moon LD, Popat RJ, King VR, Bennett GS, Patel PN, Fawcett JW, McMahon SB (2002) Chondroitinase ABC promotes functional recovery after spinal cord injury. Nature 416:636-640 (Pubitemid 34406764)
21. Bregman BS, Kunkel-Bagden E, Reier PJ, Dai HN, McAtee M, Gao D (1993) 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 123:3-16 (Pubitemid 23294570)
22. Brock JH, Rosenzweig ES, Blesch A, Moseanko R, Havton LA, Edgerton VR, Tuszynski MH (2010) Local and remote growth factor effects after primate spinal cord injury. J Neurosci 30:9728-9737
23. Cafferty WB, Gardiner NJ, Das P, Qiu J, McMahon SB, Thompson SW (2004) Conditioning injury-induced spinal axon regeneration fails in interleukin-6 knock-out mice. J Neurosci 24:4432-4443 (Pubitemid 38608154)
24. Cai D, Qiu J, Cao Z, McAtee M, Bregman BS, Filbin MT (2001) Neuronal cyclic AMP controls the developmental loss in ability of axons to regenerate. J Neurosci 21:4731-4739 (Pubitemid 32565631)
25. Campenot RB (1982) Development of sympathetic neurons in compartmentalized cultures. Il Local control of neurite growth by nerve growth factor. Dev Biol 93:1-12
26. Cao Z, Gao Y, Bryson JB, Hou J, Chaudhry N, Siddiq M, Martinez J, Spencer T, Carmel J, Hart RB, Filbin MT (2006) The cytokine interleukin-6 is sufficient but not necessary to mimic the peripheral conditioning lesion effect on axonal growth. J Neurosci 26:5565-5573 (Pubitemid 44318407)
27. Chau CH, Shum DK, Li H, Pei J, Lui YY, Wirthlin L, Chan YS, Xu XM (2004) Chondroitinase ABC enhances axonal regrowth through Schwann cell-seeded guidance channels after spinal cord injury. FASEB J 18:194-196
28. Costigan M, Befort K, Karchewski L, Griffin RS, D'Urso D, Allchorne A, Sitarski J, Mannion JW, Pratt RE, Woolf CJ (2002) Replicate high-density rat genome oligonucleotide microarrays reveal hundreds of regulated genes in the dorsal root ganglion after peripheral nerve injury. BMC Neurosci 3:16
29. Coumans JV, Lin TT, Dai HN, MacArthur L, McAtee M, Nash C and Bregman BS (2001) Axonal regeneration and functional recovery after complete spinal cord transection in rats by delayed treatment with transplants and neurotrophins. J Neurosci 21:9334-9344 (Pubitemid 33096877)
30. Courtine G, Song B, Roy RR, Zhong H, Herrmann JE, Ao Y, Qi J, Edgerton VR, Sofroniew MV (2008) Recovery of supraspinal control of stepping via indirect propriospinal relay connections after spinal cord injury. Nat Med 14:69-74
31. Cui Q (2006) Actions of neurotrophic factors and their signaling pathways in neuronal survival and axonal regeneration. Mol Neurobiol 33:155-179
32. David S, Aguayo AJ (1981) Axonal elongation into peripheral nervous system "bridges" after central nervous system injury in adult rats. Science 214:931-933 (Pubitemid 12220099)
33. Dergham P, Ellezam B, Essagian C, Avedissian H, Lubell WD, McKerracher L (2002) Rho signaling pathway targeted to promote spinal cord repair. J Neurosci 22:6570-6577 (Pubitemid 35386413)
34. English AW, Meador W, Carrasco DI (2005) Neurotrophin-4/5 is required for the early growth of regenerating axons in peripheral nerves. Eur J Neurosci 21:2624-2634 (Pubitemid 40835106)
35. Fitch MT, Silver J (2008) CNS injury, glial scars, and inflammation: inhibitory extracellular matrices and regeneration failure. Exp Neurol 209:294-301 (Pubitemid 351174127)
36. Fortun J, Puzis R, Pearse DD, Gage FH, Bunge MB (2009) Muscle injection of AAV-NT3 promotes anatomical reorganization of CST axons and improves behavioral outcome following SCI. J Neurotrauma 26:941-953
37. Fouad K, Pedersen V, Schwab ME, Brosamle C (2001) Cervical sprouting of corticospinal fibers after thoracic spinal cord injury accompanies shifts in evoked motor responses. Curr Biol 11:1766-1770 (Pubitemid 33092164)
38. Fouad K, Schnell L, Bunge MB, Schwab ME, Liebscher T, Pearse DD (2005) Combining Schwann cell bridges and olfactoryensheathing glia grafts with chondroitinase promotes locomotor recovery after complete transection of the spinal cord. J Neurosci 25:1169-1178 (Pubitemid 40268958)
39. Funakoshi H, Frisen J, Barbany G, Timmusk T, Zachrisson O, Verge VM, Persson H (1993) Differential expression of mRNAs for neurotrophins and their receptors after axotomy of the sciatic nerve. J Cell Biol 123:455-465 (Pubitemid 23313968)
40. Galtrey CM, Kwok JC, Carulli D, Rhodes KE, Fawcett JW (2008) Distribution and synthesis of extracellular matrix proteoglycans, hyaluronan, link proteins and tenascin-R in the rat spinal cord. Eur J Neurosci 27:1373-1390 (Pubitemid 351406265)
41. Gao Y, Deng K, Hou J, Bryson JB, Barco A, Nikulina E, Spencer T, Mellado W, Kandel ER, Filbin MT (2004) Activated CREB is sufficient to overcome inhibitors in myelin and promote spinal axon regeneration in vivo. Neuron 44:609-621 (Pubitemid 39531226)
42. Garcia-Alias G, Barkhuysen S, Buckle M, Fawcett JW (2009) Chondroitinase ABC treatment opens a window of opportunity for task-specific rehabilitation. Nat Neurosci 12:1145-1151
43. Geremia NM, Pettersson LM, Hasmatali JC, Hryciw T, Danielsen N, Schreyer DJ, Verge VM (2010) Endogenous BDNF regulates induction of intrinsic neuronal growth programs in injured sensory neurons. Exp Neurol 223:128-142
44. Giehl KM, Tetzlaff W (1996) BDNF and NT-3, but not NGF, prevent axotomy-induced death of rat corticospinal neurons in vivo. Eur J Neurosci 8:1167-1175 (Pubitemid 26174643)
45. Giger RJ, Hollis ER 2nd, Tuszynski MH (2010) Guidance molecules in axon regeneration. Cold Spring Harb Perspect Biol 2:a001867
46. Girgis J, Merrett D, Kirkland S, Metz GA, Verge V, Fouad K (2007) Reaching training in rats with spinal cord injury promotes plasticity and task specific recovery. Brain 130:2993-3003 (Pubitemid 350033978)
47. Goldberg JL, Klassen MP, Hua Y, Barres BA (2002) Amacrine-signaled loss of intrinsic axon growth ability by retinal ganglion cells. Science 296:1860-1864 (Pubitemid 34596271)
48. Gomez-Pinilla F, Ying Z, Roy RR, Molteni R, Edgerton VR (2002) Voluntary exercise induces a BDNF-mediated mechanism that promotes neuroplasticity. J Neurophysiol 88:2187-2195 (Pubitemid 35346024)
49. Grill R, Murai K, Blesch A, Gage FH, Tuszynski MH (1997) Cellular delivery of neurotrophin-3 promotes corticospinal axonal growth and partial functional recovery after spinal cord injury. J Neurosci 17:5560-5572 (Pubitemid 127777377)
50. Gros T, Sakamoto JS, Blesch A, Havton LA, Tuszynski MH (2010) Regeneration of long-tract axons through sites of spinal cord injury using templated agarose scaffolds. Biomaterials 31:6719-6729
51. Gundersen RW, Barrett JN (1979) Neuronal chemotaxis: chick dorsal-root axons turn toward high concentrations of nerve growth factor. Science 206:1079-1080 (Pubitemid 10208880)
52. Hannila SS, Filbin MT (2008) The role of cyclic AMP signaling in promoting axonal regeneration after spinal cord injury. Exp Neurol 209:321-332 (Pubitemid 351174133)
53. Hanz S, Perlson E, Willis D, Zheng JQ, Massarwa R, Huerta JJ, Koltzenburg M, Kohler M, van-Minnen J, Twiss JL, Fainzilber M (2003) Axoplasmic importins enable retrograde injury signaling in lesioned nerve. Neuron 40:1095-1104 (Pubitemid 38032787)
54. Heumann R, Lindholm D, Bandtlow C, Meyer M, Radeke MJ, Misko TP, Shooter E, Thoenen H (1987) Differential regulation of mRNA encoding nerve growth factor and its receptor in rat sciatic nerve during development, degeneration, and regeneration: role of macrophages. Proc Natl Acad Sci USA 84:8735-8739
55. Hofstetter CP, Schwarz EJ, Hess D,Widenfalk J, El Manira A, Prockop DJ, Olson L (2002) Marrow stromal cells form guiding strands in the injured spinal cord and promote recovery. Proc Natl Acad Sci USA 99:2199-2204 (Pubitemid 34169038)
56. Hollis ER 2nd, Jamshidi P, Low K, Blesch A, Tuszynski MH (2009) Induction of corticospinal regeneration by lentiviral trkB-induced Erk activation. Proc Natl Acad Sci USA 106:7215-7220
57. Houle JD, Tom VJ, Mayes D, Wagoner G, Phillips N, Silver J (2006) Combining an autologous peripheral nervous system "bridge" and matrix modification by chondroitinase allows robust, functional regeneration beyond a hemisection lesion of the adult rat spinal cord. J Neurosci 26:7405-7415 (Pubitemid 44315209)
58. Hu X, Cai J, Yang J, Smith GM (2010) Sensory axon targeting is increased by NGF gene therapy within the lesioned adult femoral nerve. Exp Neurol 223:153-165
59. Hutchinson KJ, Gomez-Pinilla F, Crowe MJ, Ying Z, Basso DM (2004) Three exercise paradigms differentially improve sensory recovery after spinal cord contusion in rats. Brain 127:1403-1414 (Pubitemid 38745518)
60. Jain A, McKeon RJ, Brady-Kalnay SM, Bellamkonda RV (2011) Sustained delivery of activated Rho GTPases and BDNF promotes axon growth in CSPG-rich regions following spinal cord injury. PLoS One 6:e16135
61. Jin Y, Ziemba KS, Smith GM (2008) Axon growth across a lesion site along a preformed guidance pathway in the brain. Exp Neurol 210:521-530
62. Jones LL, Margolis RU, Tuszynski MH (2003) The chondroitin sulfate proteoglycans neurocan, brevican, phosphacan, and versican are differentially regulated following spinal cord injury. Exp Neurol 182:399-411 (Pubitemid 36937092)
63. Kadoya K, Tsukada S, Lu P, Coppola G, Geschwind D, Filbin M, Blesch A, Tuszynski MH (2009) Combined intrinsic and extrinsic neuronal mechanisms facilitate bridging axonal regeneration one year after spinal cord injury. Neuron 64:165-172
64. Karimi-Abdolrezaee S, Eftekharpour E, Wang J, Schut D, Fehlings MG (2010) Synergistic effects of transplanted adult neural stem/ progenitor cells, chondroitinase, and growth factors promote functional repair and plasticity of the chronically injured spinal cord. J Neurosci 30:1657-1676
65. Kimpinski K, Campenot RB, Mearow K (1997) Effects of the neurotrophins nerve growth factor, neurotrophin-3, and brain-derived neurotrophic factor (BDNF) on neurite growth from adult sensory neurons in compartmented cultures. J Neurobiol 33:395-410 (Pubitemid 27411220)
66. Kobayashi NR, Fan DP, Giehl KM, Bedard AM, Wiegand SJ, Tetzlaff W (1997) 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 17:9583-9595 (Pubitemid 28006402)
67. Kuo HS, Tsai MJ, Huang MC, Chiu CW, Tsai CY, Lee MJ, Huang WC, Lin YL, Kuo WC, Cheng H (2011) Acid fibroblast growth factor and peripheral nerve grafts regulate Th2 cytokine expression, macrophage activation, polyamine synthesis, and neurotrophin expression in transected rat spinal cords. J Neurosci 31:4137-4147
68. Kwon BK, Liu J, Messerer C, Kobayashi NR, McGraw J, Oschipok L, Tetzlaff W (2002) Survival and regeneration of rubrospinal neurons 1 year after spinal cord injury. Proc Natl Acad Sci USA 99:3246-3251 (Pubitemid 34240617)
69. Kwon BK, Liu J, Lam C, Plunet W, Oschipok LW, Hauswirth W, Di Polo A, Blesch A, Tetzlaff W (2007) 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 32:1164-1173 (Pubitemid 46743016)
70. Lee H, McKeon RJ, Bellamkonda RV (2010) Sustained delivery of thermostabilized chABC enhances axonal sprouting and functional recovery after spinal cord injury. Proc Natl Acad Sci USA 107:3340-3345
71. Lepore AC, Fischer I (2005) Lineage-restricted neural precursors survive, migrate, and differentiate following transplantation into the injured adult spinal cord. Exp Neurol 194:230-242 (Pubitemid 40719758)
72. Li Y, Raisman G (1994) Schwann cells induce sprouting in motor and sensory axons in the adult rat spinal cord. J Neurosci 14:4050-4063 (Pubitemid 24200532)
73. Li Y, Field M, Raisman G (1997) Repair of adult rat corticospinal tract by transplants of olfactory ensheathing cells. Science 277:2000-2002 (Pubitemid 27449143)
74. Liu Y, Kim D, Himes BT, Chow SY, Schallert T, Murray M, Tessler A, Fischer I (1999) 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 19:4370-4387 (Pubitemid 29241090)
75. Liu K, Lu Y, Lee JK, Samara R, Willenberg R, Sears-Kraxberger I, Tedeschi A, Park KK, Jin D, Cai B, Xu B, Connolly L, Steward O, Zheng B, He Z (2010) PTEN deletion enhances the regenerative ability of adult corticospinal neurons. Nat Neurosci 13:1075-1081
76. Lu P, Blesch A, Tuszynski MH (2001) Neurotrophism without neurotropism: BDNF promotes survival but not growth of lesioned corticospinal neurons. J Comp Neurol 436:456-470 (Pubitemid 32623064)
77. Lu P, Jones LL, Snyder EY, Tuszynski MH (2003) Neural stem cells constitutively secrete neurotrophic factors and promote extensive host axonal growth after spinal cord injury. Exp Neurol 181:115-129 (Pubitemid 36629234)
78. Lu P, Yang H, Jones LL, Filbin MT, Tuszynski MH (2004) Combinatorial therapy with neurotrophins and cAMP promotes axonal regeneration beyond sites of spinal cord injury. J Neurosci 24:6402-6409 (Pubitemid 38944231)
79. Lu P, Jones LL, Tuszynski MH (2005) BDNF-expressing marrow stromal cells support extensive axonal growth at sites of spinal cord injury. Exp Neurol 191:344-360 (Pubitemid 40092879)
80. Lu P, Yang H, Culbertson M, Graham L, Roskams AJ, Tuszynski MH (2006) Olfactory ensheathing cells do not exhibit unique migratory or axonal growth-promoting properties after spinal cord injury. J Neurosci 26:11120-11130 (Pubitemid 44772200)
81. Massey JM, Amps J, Viapiano MS, Matthews RT, Wagoner MR, Whitaker CM, Alilain W, Yonkof AL, Khalyfa A, Cooper NG, Silver J, Onifer SM (2008) 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 209:426-445 (Pubitemid 351174125)
82. Menei P, Montero-Menei C, Whittemore SR, Bunge RP, Bunge MB (1998) Schwann cells genetically modified to secrete human BDNF promote enhanced axonal regrowth across transected adult rat spinal cord. Eur J Neurosci 10:607-621 (Pubitemid 28325484)
83. Meyer M, Matsuoka I, Wetmore C, Olson L, Thoenen H (1992) Enhanced synthesis of brain-derived neurotrophic factor in the lesioned peripheral nerve: different mechanisms are responsible for the regulation of BDNF and NGF mRNA. J Cell Biol 119:45-54
84. Michaelevski I, Segal-Ruder Y, Rozenbaum M, Medzihradszky KF, Shalem O, Coppola G, Horn-Saban S, Ben-Yaakov K, Dagan SY, Rishal I, Geschwind DH, Pilpel Y, Burlingame AL, Fainzilber M (2010) Signaling to transcription networks in the neuronal retrograde injury response. Sci Signal 3:ra53
85. Moore DL, Blackmore MG, Hu Y, Kaestner KH, Bixby JL, Lemmon VP, Goldberg JL (2009) KLF family members regulate intrinsic axon regeneration ability. Science 326:298-301
86. Mori F, Himes BT, Kowada M, Murray M, Tessler A (1997) Fetal spinal cord transplants rescue some axotomized rubrospinal neurons from retrograde cell death in adult rats. Exp Neurol 143:45-60 (Pubitemid 27049131)
87. Muller A, Hauk TG, Leibinger M, Marienfeld R, Fischer D (2009) Exogenous CNTF stimulates axon regeneration of retinal ganglion cells partially via endogenous CNTF. Mol Cell Neurosci 41:233-246
88. Naveilhan P, ElShamy WM, Ernfors P (1997) Differential regulation of mRNAs for GDNF and its receptors Ret and GDNFR alpha after sciatic nerve lesion in the mouse. Eur J Neurosci 9:1450-1460 (Pubitemid 27303245)
89. Neet KE, Campenot RB (2001) Receptor binding, internalization, and retrograde transport of neurotrophic factors. Cell Mol Life Sci 58:1021-1035 (Pubitemid 32756513)
90. Neumann S, Woolf CJ (1999) Regeneration of dorsal column fibers into and beyond the lesion site following adult spinal cord injury. Neuron 23:83-91 (Pubitemid 29262466)
91. Neumann S, Bradke F, Tessier-Lavigne M, Basbaum AI (2002) Regeneration of sensory axons within the injured spinal cord induced by intraganglionic cAMP elevation. Neuron 34:885-893 (Pubitemid 34722279)
92. Nielson JL, Strong MK, Steward O (2011) A reassessment of whether cortical motor neurons die following spinal cord injury. J Comp Neurol 519:2852-2869
93. Nikulina E, Tidwell JL, Dai HN, Bregman BS, Filbin MT (2004) The phosphodiesterase inhibitor rolipram delivered after a spinal cord lesion promotes axonal regeneration and functional recovery. Proc Natl Acad Sci USA 101:8786-8790 (Pubitemid 38745849)
94. Park KK, Liu K, Hu Y, Smith PD, Wang C, Cai B, Xu B, Connolly L, Kramvis I, Sahin M, He Z (2008) Promoting axon regeneration in the adult CNS by modulation of the PTEN/mTOR pathway. Science 322:963-966
95. Pearse DD, Pereira FC, Marcillo AE, Bates ML, Berrocal YA, Filbin MT Bunge MB (2004)cAMP and Schwann cells promote axonal growth and functional recovery after spinal cord injury.Nat Med 10:610-616 (Pubitemid 38796852)
96. Pfeifer K, Vroemen M, Blesch A, Weidner N (2004) Adult neural progenitor cells provide a permissive guiding substrate for corticospinal axon growth following spinal cord injury. Eur J Neurosci 20:1695-1704 (Pubitemid 39471562)
97. Popovich P, McTigue D (2009) Damage control in the nervous system: beware the immune system in spinal cord injury. Nat Med 15:736-737
98. Prang P, Muller R, Eljaouhari A, Heckmann K, Kunz W, Weber T, Faber C, Vroemen M, Bogdahn U, Weidner N (2006) The promotion of oriented axonal regrowth in the injured spinal cord by alginate-based anisotropic capillary hydrogels. Biomaterials 27:3560-3569
99. Qiu J, Cai D, Dai H, McAtee M, Hoffman PN, Bregman BS, Filbin MT (2002) Spinal axon regeneration induced by elevation of cyclic AMP. Neuron 34:895-903 (Pubitemid 34722280)
100. Qiu J, Cafferty WB, McMahon SB, Thompson SW (2005) Conditioning injury-induced spinal axon regeneration requires signal transducer and activator of transcription 3 activation. J Neurosci 25:1645-1653 (Pubitemid 40279269)
101. Ramon-Cueto A, Nieto-Sampedro M (1994) Regeneration into the spinal cord of transected dorsal root axons is promoted by ensheathing glia transplants. Exp Neurol 127:232-244 (Pubitemid 24247967)
102. Ramon-Cueto A, Cordero MI, Santos-Benito FF, Avila J (2000) Functional recovery of paraplegic rats and motor axon regeneration in their spinal cords by olfactory ensheathing glia. Neuron 25:425-435
103. Richardson PM, Issa VM (1984) Peripheral injury enhances central regeneration of primary sensory neurones. Nature 309:791-793 (Pubitemid 14119428)
104. Richardson PM, McGuinness UM, Aguayo AJ (1980) Axons from CNS neurons regenerate into PNS grafts. Nature 284:264-265 (Pubitemid 10112047)
105. Richardson PM, Issa VM, Aguayo AJ (1984) Regeneration of long spinal axons in the rat. J Neurocytol 13:165-182 (Pubitemid 14196341)
106. Richter MW, Roskams AJ (2008) Olfactory ensheathing cell transplantation following spinal cord injury: hype or hope? Exp Neurol 209:353-367 (Pubitemid 351174130)
107. Romero MI, Rangappa N, Li L, Lightfoot E, Garry MG, Smith GM (2000) Extensive sprouting of sensory afferents and hyperalgesia induced by conditional expression of nerve growth factor in the adult spinal cord. J Neurosci 20:4435-4445 (Pubitemid 30396608)
108. Rosenzweig ES, Courtine G, Jindrich DL, Brock JH, Ferguson AR, Strand SC, Nout YS, Roy RR, Miller DM, Beattie MS, Havton LA, Bresnahan JC, Edgerton VR, Tuszynski MH (2010) Extensive spontaneous plasticity of corticospinal projections after primate spinal cord injury. Nat Neurosci 13:1505-1510
109. Ruitenberg MJ, Blits B, Dijkhuizen PA, te Beek ET, Bakker A, van Heerikhuize JJ, Pool CW, Hermens WT, Boer GJ, Verhaagen J (2004) 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 15:394-406 (Pubitemid 38304891)
110. Schnell L, Schneider R, Kolbeck R, Barde YA, Schwab ME (1994) Neurotrophin-3 enhances sprouting of corticospinal tract during development and after adult spinal cord lesion. Nature 367:170-173 (Pubitemid 24031697)
111. Sendtner M, Stockli KA, Thoenen H (1992) Synthesis and localization of ciliary neurotrophic factor in the sciatic nerve of the adult rat after lesion and during regeneration. J Cell Biol 118:139-148
112. Sharp KG, Flanagan LA, Yee KM, Steward O (2010) A re-assessment of a combinatorial treatment involving Schwann cell transplants and elevation of cyclic AMP on recovery of motor function following thoracic spinal cord injury in rats.Exp Neurol 233:625-644
113. Silver J, Miller JH (2004) Regeneration beyond the glial scar. Nat Rev Neurosci 5:146-156 (Pubitemid 38160289)
114. Stam FJ, MacGillavry HD, Armstrong NJ, de Gunst MC, Zhang Y, van Kesteren RE, Smit AB, Verhaagen J (2007) Identification of candidate transcriptional modulators involved in successful regeneration after nerve injury. Eur J Neurosci 25:3629-3637 (Pubitemid 47020443)
115. Stokes BT, Reier PJ (1992) Fetal grafts alter chronic behavioral outcome after contusion damage to the adult rat spinal cord. Exp Neurol 116:1-12
116. Stokols S, Sakamoto J, Breckon C, Holt T, Weiss J, Tuszynski MH (2006) Templated agarose scaffolds support linear axonal regeneration. Tissue Eng 12:2777-2787 (Pubitemid 46141246)
117. Straley KS, Foo CW, Heilshorn SC (2010) Biomaterial design strategies for the treatment of spinal cord injuries. J Neurotrauma 27:1-19
118. Sun F, Park KK, Belin S, Wang D, Lu T, Chen G, Zhang K, Yeung C, Feng G, Yankner BA, He Z (2011) Sustained axon regeneration induced by co-deletion of PTEN and SOCS3. Nature 480:372-375
119. Tang XQ, Tanelian DL, Smith GM (2004) Semaphorin3A inhibits nerve growth factor-induced sprouting of nociceptive afferents in adult rat spinal cord. J Neurosci 24:819-827 (Pubitemid 38146592)
120. Taylor L, Jones L, Tuszynski MH, Blesch A (2006) Neurotrophin-3 gradients established by lentiviral gene delivery promote short-distance axonal bridging beyond cellular grafts in the injured spinal cord. J Neurosci 26:9713-9721 (Pubitemid 44427710)
121. Tessler A (1991) Intraspinal transplants. Ann Neurol 29:115-123
122. Tessler A, Fischer I, Giszter S, Himes BT, Miya D, Mori F, Murray M (1997) Embryonic spinal cord transplants enhance locomotor performance in spinalized newborn rats. Adv Neurol 72:291-303
123. Tetzlaff W, Okon EB, Karimi-Abdolrezaee S, Hill CE, Sparling JS, Plemel JR, Plunet WT, Tsai EC, Baptiste D, Smithson LJ, Kawaja MD, Fehlings MG, Kwon BK (2011) A systematic review of cellular transplantation therapies for spinal cord injury. J Neurotrauma 28:1611-1682
124. Tom VJ, Houle JD (2008) Intraspinal microinjection of chondroitinase ABC following injury promotes axonal regeneration out of a peripheral nerve graft bridge. Exp Neurol 211:315-319
125. Tom VJ, Sandrow-Feinberg HR, Miller K, Santi L, Connors T, Lemay MA, Houle JD (2009) Combining peripheral nerve grafts and chondroitinase promotes functional axonal regeneration in the chronically injured spinal cord. J Neurosci 29:14881-14890
126. Trupp M, Belluardo N, Funakoshi H, Ibanez CF (1997) Complementary and overlapping expression of glial cell line-derived neurotrophic factor (GDNF), c-ret proto-oncogene, and GDNF receptor-alpha indicates multiple mechanisms of trophic actions in the adult rat CNS. J Neurosci 17:3554-3567
127. Tuszynski MH, Gabriel K, Gage FH, Suhr S, Meyer S, Rosetti A (1996) Nerve growth factor delivery by gene transfer induces differential outgrowth of sensory, motor, and noradrenergic neurites after adult spinal cord injury. Exp Neurol 137:157-173 (Pubitemid 26041792)
128. Tuszynski MH, Weidner N, McCormack M, Miller I, Powell H, Conner J (1998) Grafts of genetically modified Schwann cells to the spinal cord: survival, axon growth, and myelination. Cell Transplant 7:187-196 (Pubitemid 28182754)
129. Vavrek R, Girgis J, Tetzlaff W, Hiebert GW, Fouad K (2006) BDNF promotes connections of corticospinal neurons onto spared descending interneurons in spinal cord injured rats. Brain 129:1534-1545 (Pubitemid 43999385)
130. Vaynman S, Gomez-Pinilla F (2005) License to run: exercise impacts functional plasticity in the intact and injured central nervous system by using neurotrophins. Neurorehabil Neural Repair 19:283-295 (Pubitemid 41705657)
131. Wang D, Ichiyama RM, Zhao R, Andrews MR, Fawcett JW (2011) Chondroitinase combined with rehabilitation promotes recovery of forelimb function in rats with chronic spinal cord injury. J Neurosci 31:9332-9344
132. Weidner N, Blesch A, Grill RJ, Tuszynski MH (1999) 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 413:495-506 (Pubitemid 29463624)
133. Weidner N, Ner A, Salimi N, Tuszynski MH (2001) Spontaneous corticospinal axonal plasticity and functional recovery after adult central nervous system injury. Proc Natl Acad Sci USA 98:3513-3518 (Pubitemid 32220876)
134. Wong LF, Yip PK, Battaglia A, Grist J, Corcoran J, Maden M, Azzouz M, Kingsman SM, Kingsman AJ, Mazarakis ND, McMahon SB (2006) Retinoic acid receptor beta2 promotes functional regeneration of sensory axons in the spinal cord. Nat Neurosci 9:243-250 (Pubitemid 43164548)
135. Wu D, Zhang Y, Bo X, Huang W, Xiao F, Zhang X, Miao T, Magoulas C, Subang MC, Richardson PM (2006) Actions of neuropoietic cytokines and cyclic AMP in regenerative conditioning of rat primary sensory neurons. Exp Neurol 204:66-76 (Pubitemid 46343726)
136. Xiao HS, Huang QH, Zhang FX, Bao L, Lu YJ, Guo C, Yang L, Huang WJ, Fu G, Xu SH, Cheng XP, Yan Q, Zhu ZD, Zhang X, Chen Z, Han ZG, Zhang X (2002) Identification of gene expression profile of dorsal root ganglion in the rat peripheral axotomy model of neuropathic pain. Proc Natl Acad Sci USA 99:8360-8365 (Pubitemid 34651057)
137. Xie F, Zheng B (2008) White matter inhibitors in CNS axon regeneration failure. Exp Neurol 209:302-312 (Pubitemid 351174134)
138. Xu XM, Guenard V, Kleitman N, Bunge MB (1994) Axonal regeneration into Schwann cell-seeded guidance channels grafted into transected adult rat spinal cord. J Comp Neurol 351:145-160
139. Xu XM, Guenard V, Kleitman N, Aebischer P, Bunge MB (1995) A combination of BDNF and NT-3 promotes supraspinal axonal regeneration into Schwann cell grafts in adult rat thoracic spinal cord. Exp Neurol 134:261-272
140. Xu XM, Chen A, Guenard V, Kleitman N, Bunge MB (1997) Bridging Schwann cell transplants promote axonal regeneration from both the rostral and caudal stumps of transected adult rat spinal cord. J Neurocytol 26:1-16 (Pubitemid 27186757)
141. Yick LW, So KF, Cheung PT, Wu WT (2004) Lithium chloride reinforces the regeneration-promoting effect of chondroitinase ABC on rubrospinal neurons after spinal cord injury. J Neurotrauma 21:932-943
142. Ying Z, Roy RR, Edgerton VR, Gomez-Pinilla F (2005) Exercise restores levels of neurotrophins and synaptic plasticity following spinal cord injury. Exp Neurol 193:411-419 (Pubitemid 40626768)
143. Yip PK, Wong LF, Pattinson D, Battaglia A, Grist J, Bradbury EJ, Maden M, McMahon SB, Mazarakis ND (2006) Lentiviral vector expressing retinoic acid receptor beta2 promotes recovery of function after corticospinal tract injury in the adult rat spinal cord. Hum Mol Genet 15:3107-3118 (Pubitemid 44605493)
144. Yip PK, Wong LF, Sears TA, Yanez-Munoz RJ, McMahon SB (2010) Cortical overexpression of neuronal calcium sensor-1 induces functional plasticity in spinal cord following unilateral pyramidal tract injury in rat. PLoS Biol 8:e1000399
145. Z'Graggen WJ, Fouad K, Raineteau O, Metz GA, Schwab ME, Kartje GL (2000) Compensatory sprouting and impulse rerouting after unilateral pyramidal tract lesion in neonatal rats. J Neurosci 20:6561-6569
146. Zhang JY, Luo XG, Xian CJ, Liu ZH, Zhou XF (2000) Endogenous BDNF is required for myelination and regeneration of injured sciatic nerve in rodents. Eur J Neurosci 12:4171-4180 (Pubitemid 32037828)
147. Zhong J, Dietzel ID, Wahle P, Kopf M, Heumann R (1999) Sensory impairments and delayed regeneration of sensory axons in interleukin-6-deficient mice. J Neurosci 19:4305-4313 (Pubitemid 29241084)
148. Zhou FQ, Snider WD (2006) Intracellular control of developmental and regenerative axon growth. Philos Trans R Soc Lond B 361:1575-1592
149. Zhou L, Baumgartner BJ, Hill-Felberg SJ, McGowen LR, Shine HD (2003) Neurotrophin-3 expressed in situ induces axonal plasticity in the adult injured spinal cord. J Neurosci 23:1424-1431 (Pubitemid 36258921)
150. Ziemba KS, Chaudhry N, Rabchevsky AG, Jin Y, Smith GM (2008) Targeting axon growth from neuronal transplants along preformed guidance pathways in the adult CNS. J Neurosci 28:340-348