BDNF: The career of a multifaceted neurotrophin in spinal cord injury

Experimental Neurology

Volumn 238, Issue 2, 2012, Pages 254-264

  Weishaupt, N ^a   Blesch, A ^b,c   Fouad, K ^a  

^a UNIVERSITY OF ALBERTA   (Canada)

^b UNIVERSITY HOSPITAL HEIDELBERG   (Germany)

^c UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Exercise; Hyperreflexia; Neuroprotection; Pain; Plasticity; Regeneration; TrkB signaling

Indexed keywords

BRAIN DERIVED NEUROTROPHIC FACTOR; NERVE GROWTH FACTOR; NEUROTROPHIN; NEUROTROPHIN 3; NEUROTROPHIN 4; PROTEIN TYROSINE KINASE; TROPOMYOSIN RELATED KINASE B; UNCLASSIFIED DRUG;

CELL REGENERATION; CELL SURVIVAL; DISEASE ASSOCIATION; EXERCISE; HYPERREFLEXIA; MOLECULAR PATHOLOGY; MYELINATION; NERVE CELL PLASTICITY; NERVE FIBER; NEUROPATHIC PAIN; NEUROPROTECTION; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; REVIEW; SIGNAL TRANSDUCTION; SPINAL CORD INJURY;

ANIMALS; BRAIN-DERIVED NEUROTROPHIC FACTOR; GENE EXPRESSION REGULATION; HUMANS; NEURONS; NEUROPROTECTIVE AGENTS; SPINAL CORD INJURIES;

EID: 84866936382     PISSN: 00144886     EISSN: 10902430     Source Type: Journal    
DOI: 10.1016/j.expneurol.2012.09.001     Document Type: Review

References (165)

1. Al-Majed A.A., Brushart T.M., Gordon T. Electrical stimulation accelerates and increases expression of BDNF and trkB mRNA in regenerating rat femoral motoneurons. Eur. J. Neurosci. 2000, 12:4381-4390.
2. Alto L.T., Havton L.A., Conner J.M., Hollis E.R., Blesch A., Tuszynski M.H. Chemotropic guidance facilitates axonal regeneration and synapse formation after spinal cord injury. Nat. Neurosci. 2009, 12:1106-1113.
3. Ankeny D.P., McTigue D.M., Guan Z., Yan Q., Kinstler O., Stokes B.T., Jakeman L.B. Pegylated brain-derived neurotrophic factor shows improved distribution into the spinal cord and stimulates locomotor activity and morphological changes after injury. Exp. Neurol. 2001, 170:85-100.
4. 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.
5. Bamber N.I., Li H., Lu X., Oudega M., Aebischer P., Xu X.M. 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.
6. Barde Y.A., Edgar D., Thoenen H. Purification of a new neurotrophic factor from mammalian brain. EMBO J. 1982, 1:549-553.
7. Baumbauer K.M., Huie J.R., Hughes A.J., Grau J.W. Timing in the absence of supraspinal input II: regularly spaced stimulation induces a lasting alteration in spinal function that depends on the NMDA receptor, BDNF release, and protein synthesis. J. Neurosci. 2009, 29:14383-14393.
8. Beaumont E., Kaloustian S., Rousseau G., Cormery B. Training improves the electrophysiological properties of lumbar neurons and locomotion after thoracic spinal cord injury in rats. Neurosci. Res. 2008, 62:147-154.
9. Bibel M., Hoppe E., Barde Y.A. Biochemical and functional interactions between the neurotrophin receptors trk and p75NTR. EMBO J. 1999, 18:616-622.
10. Biggs J.E., Lu V.B., Stebbing M.J., Balasubramanyan S., Smith P.A. Is BDNF sufficient for information transfer between microglia and dorsal horn neurons during the onset of central sensitization?. Mol. Pain 2010, 6:44.
11. Blesch A., Yang H., Weidner N., Hoang A., Otero D. Axonal responses to cellularly delivered NT-4/5 after spinal cord injury. Mol. Cell. Neurosci. 2004, 27:190-201.
12. Blesch A., Lu P., Tsukada S., Alto L.T., Roet K., Coppola G., Geschwind D., Tuszynski M.H. Conditioning lesions before or after spinal cord injury recruit broad genetic mechanisms that sustain axonal regeneration: superiority to camp-mediated effects. Exp. Neurol. 2011, 235:162-173.
13. Blits B., Carlstedt T.P., Ruitenberg M.J., de Winter F., Hermens W.T., Dijkhuizen P.A., Claasens J.W., Eggers R., van der Sluis R., Tenenbaum L., Boer G.J., Verhaagen J. Rescue and sprouting of motoneurons following ventral root avulsion and reimplantation combined with intraspinal adeno-associated viral vector-mediated expression of glial cell line-derived neurotrophic factor or brain-derived neurotrophic factor. Exp. Neurol. 2004, 189:303-316.
14. Blum R., Konnerth A. Neurotrophin-mediated rapid signalling in the central nervous system: mechanisms and functions. Physiology (Bethesda) 2005, 20:70-78.
15. Bonner J.F., Blesch A., Neuhuber B., Fischer I. Promoting directional axon growth from neural progenitors grafted into the injured spinal cord. J. Neurosci. Res. 2010, 88:1182-1192.
16. Bonner J.F., Connors T.M., Silverman W.F., Kowalski D.P., Lemay M.A., Fischer I. Grafted neural progenitors integrate and restore synaptic connectivity across the injured spinal cord. J. Neurosci. 2011, 31:4675-4686.
17. Boulenguez P., Liabeuf S., Bos R., Bras H., Jean-Xavier C., Brocard C., Stil A., Darbon P., Cattaert D., Delpire E., Marsala M., Vinay L. Down-regulation of the potassium-chloride cotransporter KCC2 contributes to spasticity after spinal cord injury. Nat. Med. 2010, 16:302-307.
18. Boyce V.S., Tumolo M., Fischer I., Murray M., Lemay M.A. Neurotrophic factors promote and enhance locomotor recovery in untrained spinalized cats. J. Neurophysiol. 2007, 98:1988-1996.
19. Boyce V.S., Park J., Gage F.H., Mendell L.M. Differential effects of brain-derived neurotrophic factor and neurotrophin-3 on hindlimb function in paraplegic rats. Eur. J. Neurosci. 2012, 35:221-232.
20. Bradbury E.J., King V.R., Simmons L.J., Priestley J.V., McMahon S.B. NT-3, but not BDNF, prevents atrophy and death of axotomized spinal cord projection neurons. Eur. J. Neurosci. 1998, 10:3058-3068.
21. Bregman B.S., McAtee M., Dai H.N., Kuhn P.L. Neurotrophic factors increase axonal growth after spinal cord injury and transplantation in the adult rat. Exp. Neurol. 1997, 148:475-494.
22. Brock J.H., Rosenzweig E.S., Blesch A., Moseanko R., Havton L.A., Edgerton V.R., Tuszynski M.H. Local and remote growth factor effects after primate spinal cord injury. J. Neurosci. 2010, 30:9728-9737.
23. Cai D., Shen Y., De Bellard M., Tang S., Filbin M.T. Prior exposure to neurotrophins blocks inhibition of axonal regeneration by MAG and myelin via a cAMP-dependent mechanism. Neuron 1999, 22:89-101.
24. Cao Q., Xu X.M., Devries W.H., Enzmann G.U., Ping P., Tsoulfas P., Wood P.M., Bunge M.B., Whittemore S.R. Functional recovery in traumatic spinal cord injury after transplantation of multineurotrophin-expressing glial-restricted precursor cells. J. Neurosci. 2005, 25:6947-6957.
25. Carlsson A., Magnusson T., Rosengren E. 5-Hydroxytryptamine of the spinal cord normally and after transection. Experientia 1963, 19:359.
26. Carvalho A.L., Caldeira M.V., Santos S.D., Duarte C.B. Role of the brain-derived neurotrophic factor at glutamatergic synapses. Br. J. Pharmacol. 2008, 153(Suppl. 1):S310-S324.
27. Clatterbuck R.E., Price D.L., Koliatsos V.E. Further characterization of the effects of brain-derived neurotrophic factor and ciliary neurotrophic factor on axotomized neonatal and adult mammalian motor neurons. J. Comp. Neurol. 1994, 342:45-56.
28. Constandil L., Aguilera R., Goich M., Hernandez A., Alvarez P., Infante C., Pelissier T. Involvement of spinal cord BDNF in the generation and maintenance of chronic neuropathic pain in rats. Brain Res. Bull. 2011, 86:454-459.
29. Cote M.P., Azzam G.A., Lemay M.A., Zhukareva V., Houle J.D. Activity-dependent increase in neurotrophic factors is associated with an enhanced modulation of spinal reflexes after spinal cord injury. J. Neurotrauma 2011, 28:299-309.
30. Coull J.A., Beggs S., Boudreau D., Boivin D., Tsuda M., Inoue K., Gravel C., Salter M.W., De Koninck Y. BDNF from microglia causes the shift in neuronal anion gradient underlying neuropathic pain. Nature 2005, 438:1017-1021.
31. Coumans J.V., Lin T.T., Dai H.N., MacArthur L., McAtee M., Nash C., Bregman B.S. Axonal regeneration and functional recovery after complete spinal cord transection in rats by delayed treatment with transplants and neurotrophins. J. Neurosci. 2001, 21:9334-9344.
32. Crutcher K.A., Gendelman H.E., Kipnis J., Perez-Polo J.R., Perry V.H., Popovich P.G., Weaver L.C. Debate: "is increasing neuroinflammation beneficial for neural repair?". J. Neuroimmune Pharmacol. 2006, 1:195-211.
33. Dechant G., Barde Y.A. The neurotrophin receptor p75(NTR): novel functions and implications for diseases of the nervous system. Nat. Neurosci. 2002, 5:1131-1136.
34. Dolcet X., Egea J., Soler R.M., Martin-Zanca D., Comella J.X. Activation of phosphatidylinositol 3-kinase, but not extracellular-regulated kinases, is necessary to mediate brain-derived neurotrophic factor-induced motoneuron survival. J. Neurochem. 1999, 73:521-531.
35. Donnelly D.J., Popovich P.G. Inflammation and its role in neuroprotection, axonal regeneration and functional recovery after spinal cord injury. Exp. Neurol. 2008, 209:378-388.
36. Eaton M.J., Blits B., Ruitenberg M.J., Verhaagen J., Oudega M. Amelioration of chronic neuropathic pain after partial nerve injury by adeno-associated viral (AAV) vector-mediated over-expression of BDNF in the rat spinal cord. Gene Ther. 2002, 9:1387-1395.
37. Endo T., Ajiki T., Inoue H., Kikuchi M., Yashiro T., Nakama S., Hoshino Y., Murakami T., Kobayashi E. Early exercise in spinal cord injured rats induces allodynia through TrkB signalling. Biochem. Biophys. Res. Commun. 2009, 381:339-344.
38. English A.W., Schwartz G., Meador W., Sabatier M.J., Mulligan A. Electrical stimulation promotes peripheral axon regeneration by enhanced neuronal neurotrophin signalling. Dev. Neurobiol. 2007, 67:158-172.
39. Fenner B.M. Truncated TrkB: beyond a dominant negative receptor. Cytokine Growth Factor Rev. 2012, 23:15-24.
40. Fouad K., Tse A. Adaptive changes in the injured spinal cord and their role in promoting functional recovery. Neurol. Res. 2008, 30:17-27.
41. Fouad K., Pedersen V., Schwab M.E., Brosamle C. Cervical sprouting of corticospinal fibers after thoracic spinal cord injury accompanies shifts in evoked motor responses. Curr. Biol. 2001, 11:1766-1770.
42. Fouad, K., Vavrek, R., Cho, S., in press. A TrkB antibody agonist promotes plasticity following cervical spinal cord injury in adult rats. J. Neurotrauma (July 2) (Electronic publication ahead of print).
43. Friedman B., Kleinfeld D., Ip N.Y., Verge V.M., Moulton R., Boland P., Zlotchenko E., Lindsay R.M., Liu L. BDNF and NT-4/5 exert neurotrophic influences on injured adult spinal motor neurons. J. Neurosci. 1995, 15:1044-1056.
44. Fritsch B., Reis J., Martinowich K., Schambra H.M., Ji Y., Cohen L.G., Lu B. Direct current stimulation promotes BDNF-dependent synaptic plasticity: potential implications for motor learning. Neuron 2010, 66:198-204.
45. Gao Y., Nikulina E., Mellado W., Filbin M.T. 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.
46. Gehler S., Gallo G., Veien E., Letourneau P.C. p75 neurotrophin receptor signalling regulates growth cone filopodial dynamics through modulating RhoA activity. J. Neurosci. 2004, 24:4363-4372.
47. Geng S.J., Liao F.F., Dang W.H., Ding X., Liu X.D., Cai J., Han J.S., Wan Y., Xing G.G. Contribution of the spinal cord BDNF to the development of neuropathic pain by activation of the NR2B-containing NMDA receptors in rats with spinal nerve ligation. Exp. Neurol. 2010, 222:256-266.
48. Geremia N.M., Pettersson L.M., Hasmatali J.C., Hryciw T., Danielsen N., Schreyer D.J., Verge V.M. Endogenous BDNF regulates induction of intrinsic neuronal growth programs in injured sensory neurons. Exp. Neurol. 2010, 223:128-142.
49. 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.
50. Girard C., Bemelmans A.P., Dufour N., Mallet J., Bachelin C., Nait-Oumesmar B., Baron-Van Evercooren A., Lachapelle F. Grafts of brain-derived neurotrophic factor and neurotrophin 3-transduced primate Schwann cells lead to functional recovery of the demyelinated mouse spinal cord. J. Neurosci. 2005, 25:7924-7933.
51. Gomez-Pinilla F., Ying Z., Roy R.R., Molteni R., Edgerton V.R. Voluntary exercise induces a BDNF-mediated mechanism that promotes neuroplasticity. J. Neurophysiol. 2002, 88:2187-2195.
52. Gomez-Pinilla F., Huie J.R., Ying Z., Ferguson A.R., Crown E.D., Baumbauer K.M., Edgerton V.R., Grau J.W. BDNF and learning: evidence that instrumental training promotes learning within the spinal cord by up-regulating BDNF expression. Neuroscience 2007, 148:893-906.
53. Gordon T. The role of neurotrophic factors in nerve regeneration. Neurosurg. Focus. 2009, 26:E3.
54. Gravel C., Götz R., Lorrain A., Sendtner M. Adenoviral gene transfer of ciliary neurotrophic factor and brain-derived neurotrophic factor leads to long-term survival of axotomized motor neurons. Nat. Med. 1997, 3:765-770.
55. Groth R., Aanonsen L. Spinal brain-derived neurotrophic factor (BDNF) produces hyperalgesia in normal mice while antisense directed against either BDNF or trkB, prevent inflammation-induced hyperalgesia. Pain 2002, 100:171-181.
56. Guo W., Robbins M.T., Wei F., Zou S., Dubner R., Ren K. Supraspinal brain-derived neurotrophic factor signalling: a novel mechanism for descending pain facilitation. J. Neurosci. 2006, 26:126-137.
57. Hagg T., Oudega M. Degenerative and spontaneous regenerative processes after spinal cord injury. J. Neurotrauma 2006, 23:264-280.
58. Hausmann O.N. Post-traumatic inflammation following spinal cord injury. Spinal Cord 2003, 41:369-378.
59. Hayashida K., Clayton B.A., Johnson J.E., Eisenach J.C. Brain derived nerve growth factor induces spinal noradrenergic fiber sprouting and enhances clonidine analgesia following nerve injury in rats. Pain 2008, 136:348-355.
60. Hempstead B.L. The many faces of p75NTR. Curr. Opin. Neurobiol. 2002, 12:260-267.
61. Hiebert G.W., Khodarahmi K., McGraw J., Steeves J.D., Tetzlaff W. 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.
62. Hollis E.R., Jamshidi P., Low K., Blesch A., Tuszynski M.H. Induction of corticospinal regeneration by lentiviral trkB-induced Erk activation. Proc. Natl. Acad. Sci. U. S. A. 2009, 106:7215-7220.
63. Houle J.D., Ye J.H. Survival of chronically-injured neurons can be prolonged by treatment with neurotrophic factors. Neuroscience 1999, 94:929-936.
64. Huie J.R., Garraway S.M., Baumbauer K.M., Hoy K.C., Beas B.S., Montgomery K.S., Bizon J.L., Grau J.W. Brain-derived neurotrophic factor promotes adaptive plasticity within the spinal cord and mediates the beneficial effects of controllable stimulation. Neuroscience 2012, 200:74-90.
65. Hultborn H., Denton M.E., Wienecke J., Nielsen J.B. Variable amplification of synaptic input to cat spinal motoneurones by dendritic persistent inward current. J. Physiol. 2003, 552:945-952.
66. Hutchinson K.J., Gomez-Pinilla F., Crowe M.J., Ying Z., Basso D.M. Three exercise paradigms differentially improve sensory recovery after spinal cord contusion in rats. Brain 2004, 127:1403-1414.
67. Ikeda O., Murakami M., Ino H., Yamazaki M., Koda M., Nakayama C., Moriya H. Effects of brain-derived neurotrophic factor (BDNF) on compression-induced spinal cord injury: BDNF attenuates down-regulation of superoxide dismutase expression and promotes up-regulation of myelin basic protein expression. J. Neuropathol. Exp. Neurol. 2002, 61:142-153.
68. Jain A., McKeon R.J., Brady-Kalnay S.M., Bellamkonda R.V. Sustained delivery of activated Rho GTPases and BDNF promotes axon growth in CSPG-rich regions following spinal cord injury. PLoS One 2011, 6:e16135.
69. Jakeman L.B., Wei P., Guan Z., Stokes B.T. Brain-derived neurotrophic factor stimulates hindlimb stepping and sprouting of cholinergic fibers after spinal cord injury. Exp. Neurol. 1998, 154:170-184.
70. Jiang Y., Wei N., Zhu J., Lu T., Chen Z., Xu G., Liu X. Effects of brain-derived neurotrophic factor on local inflammation in experimental stroke of rat. Mediat. Inflamm. 2010, 2010:372423.
71. Jiang Y., Wei N., Lu T., Zhu J., Xu G., Liu X. Intranasal brain-derived neurotrophic factor protects brain from ischemic insult via modulating local inflammation in rats. Neuroscience 2011, 172:398-405.
72. Jin Y., Tessler A., Fischer I., Houle J.D. Fibroblasts genetically modified to produce BDNF support regrowth of chronically injured serotonergic axons. Neurorehabil. Neural Repair 2000, 14:311-317.
73. Jin Y., Fischer I., Tessler A., Houle J.D. Transplants of fibroblasts genetically modified to express BDNF promote axonal regeneration from supraspinal neurons following chronic spinal cord injury. Exp. Neurol. 2002, 177:265-275.
74. Johnson J.E., Barde Y.A., Schwab M., Thoenen H. Brain-derived neurotrophic factor supports the survival of cultured rat retinal ganglion cells. J. Neurosci. 1986, 6:3031-3038.
75. Joosten E.A., Houweling D.A. Local acute application of BDNF in the lesioned spinal cord anti-inflammatory and anti-oxidant effects. Neuroreport 2004, 15:1163-1166.
76. Jordan L.M., Liu J., Hedlund P.B., Akay T., Pearson K.G. Descending command systems for the initiation of locomotion in mammals. Brain Res. Rev. 2008, 57:183-191.
77. Kafitz K.W., Rose C.R., Thoenen H., Konnerth A. Neurotrophin-evoked rapid excitation through TrkB receptors. Nature 1999, 401:918-921.
78. Kaplan D.R., Miller F.D. Neurotrophin signal transduction in the nervous system. Curr. Opin. Neurobiol. 2000, 10:381-391.
79. Ke Z., Yip S.P., Li L., Zheng X.X., Tong K.Y. The effects of voluntary, involuntary, and forced exercises on brain-derived neurotrophic factor and motor function recovery: a rat brain ischemia model. PLoS One 2011, 6:e16643.
80. Kerr B.J., Bradbury E.J., Bennett D.L., Trivedi P.M., Dassan P., French J., Shelton D.B., McMahon S.B., Thompson S.W. Brain-derived neurotrophic factor modulates nociceptive sensory inputs and NMDA-evoked responses in the rat spinal cord. J. Neurosci. 1999, 19:5138-5148.
81. King V.R., Michael G.J., Joshi R.K., Priestley J.V. trkA, trkB, and trkC messenger RNA expression by bulbospinal cells of the rat. Neuroscience 1999, 92:935-944.
82. King V.R., Bradbury E.J., McMahon S.B., Priestley J.V. Changes in truncated trkB and p75 receptor expression in the rat spinal cord following spinal cord hemisection and spinal cord hemisection plus neurotrophin treatment. Exp. Neurol. 2000, 165:327-341.
83. Kishino A., Ishige Y., Tatsuno T., Nakayama C., Noguchi H. BDNF prevents and reverses adult rat motor neuron degeneration and induces axonal outgrowth. Exp. Neurol. 1997, 144:273-286.
84. Kobayashi N.R., Fan D.P., Giehl K.M., Bedard A.M., Wiegand S.J., Tetzlaff W. 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.
85. Koda M., Murakami M., Ino H., Yoshinaga K., Ikeda O., Hashimoto M., Yamazaki M., Nakayama C., Moriya H. Brain-derived neurotrophic factor suppresses delayed apoptosis of oligodendrocytes after spinal cord injury in rats. J. Neurotrauma 2002, 19:777-785.
86. Koda M., Hashimoto M., Murakami M., Yoshinaga K., Ikeda O., Yamazaki M., Koshizuka S., Kamada T., Moriya H., Shirasawa H., Sakao S., Ino H. Adenovirus vector-mediated in vivo gene transfer of brain-derived neurotrophic factor (BDNF) promotes rubrospinal axonal regeneration and functional recovery after complete transection of the adult rat spinal cord. J. Neurotrauma 2004, 21:329-337.
87. Koliatsos V.E., Clatterbuck R.E., Winslow J.W., Cayouette M.H., Price D.L. Evidence that brain-derived neurotrophic factor is a trophic factor for motor neurons in vivo. Neuron 1993, 10:359-367.
88. Kwon B.K., Liu J., Messerer C., Kobayashi N.R., McGraw J., Oschipok L., Tetzlaff W. Survival and regeneration of rubrospinal neurons 1year after spinal cord injury. Proc. Natl. Acad. Sci. U. S. A. 2002, 99:3246-3251.
89. Kwon B.K., Liu J., Oschipok L., Teh J., Liu Z.W., Tetzlaff W. Rubrospinal neurons fail to respond to brain-derived neurotrophic factor applied to the spinal cord injury site 2months after cervical axotomy. Exp. Neurol. 2004, 189:45-57.
90. Kwon B.K., Tetzlaff W., Grauer J.N., Beiner J., Vaccaro A.R. Pathophysiology and pharmacologic treatment of acute spinal cord injury. Spine J. 2004, 4:451-464.
91. Kwon B.K., Liu J., Lam C., Plunet W., Oschipok L.W., Hauswirth W., Di Polo A., Blesch A., Tetzlaff W. 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.
92. Lang E.M., Schlegel N., Reiners K., Hofmann G.O., Sendtner M., Asan E. Single-dose application of CNTF and BDNF improves remyelination of regenerating nerve fibers after C7 ventral root avulsion and replantation. J. Neurotrauma 2008, 25:384-400.
93. Lee R., Kermani P., Teng K.K., Hempstead B.L. Regulation of cell survival by secreted proneurotrophins. Science 2001, 294:1945-1948.
94. Lehmann M., Fournier A., Selles-Navarro I., Dergham P., Sebok A., Leclerc N., Tigyi G., McKerracher L. Inactivation of Rho signalling pathway promotes CNS axon regeneration. J. Neurosci. 1999, 19:7537-7547.
95. Lever I.J., Bradbury E.J., Cunningham J.R., Adelson D.W., Jones M.G., McMahon S.B., Marvizon J.C., Malcangio M. Brain-derived neurotrophic factor is released in the dorsal horn by distinctive patterns of afferent fiber stimulation. J. Neurosci. 2001, 21:4469-4477.
96. Liebl D.J., Huang W., Young W., Parada L.F. Regulation of Trk receptors following contusion of the rat spinal cord. Exp. Neurol. 2001, 167:15-26.
97. Lin Y.T., Ro L.S., Wang H.L., Chen J.C. Up-regulation of dorsal root ganglia BDNF and trkB receptor in inflammatory pain: an in vivo and in vitro study. J. Neuroinflammation 2011, 8:126.
98. Liu Y., Kim D., Himes B.T., Chow S.Y., Schallert T., Murray M., Tessler A., Fischer I. Transplants of fibroblasts genetically modified to express BDNF promote regeneration of adult rat rubrospinal axons and recovery of forelimb function. J. Neurosci. 1999, 19:4370-4387.
99. Liu Y., Himes B.T., Murray M., Tessler A., Fischer I. Grafts of BDNF-producing fibroblasts rescue axotomized rubrospinal neurons and prevent their atrophy. Exp. Neurol. 2002, 178:150-164.
100. 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.
101. Lu B., Pang P.T., Woo N.H. The yin and yang of neurotrophin action. Nat. Rev. Neurosci. 2005, 6:603-614.
102. 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.
103. Lu V.B., Ballanyi K., Colmers W.F., Smith P.A. Neuron type-specific effects of brain-derived neurotrophic factor in rat superficial dorsal horn and their relevance to 'central sensitization'. J. Physiol. 2007, 584:543-563.
104. Lu Y., Christian K., Lu B. BDNF: a key regulator for protein synthesis-dependent LTP and long-term memory?. Neurobiol. Learn. Mem. 2008, 89:312-323.
105. Lu V.B., Biggs J.E., Stebbing M.J., Balasubramanyan S., Todd K.G., Lai A.Y., Colmers W.F., Dawbarn D., Ballanyi K., Smith P.A. Brain-derived neurotrophic factor drives the changes in excitatory synaptic transmission in the rat superficial dorsal horn that follow sciatic nerve injury. J. Physiol. 2009, 587:1013-1032.
106. Lu P., Blesch A., Graham L., Wang Y., Samara R., Banos K., Haringer V., Havton L., Weishaupt N., Bennett D., Fouad K., Tuszynski M.H. Motor axonal regeneration after partial and complete spinal cord transection. J. Neurosci. 2012, 32:8208-8218.
107. Macias M., Nowicka D., Czupryn A., Sulejczak D., Skup M., Skangiel-Kramska J., Czarkowska-Bauch J. Exercise-induced motor improvement after complete spinal cord transection and its relation to expression of brain-derived neurotrophic factor and presynaptic markers. BMC Neurosci. 2009, 10:144.
108. Madara J.C., Levine E.S. Presynaptic and postsynaptic NMDA receptors mediate distinct effects of brain-derived neurotrophic factor on synaptic transmission. J. Neurophysiol. 2008, 100:3175-3184.
109. Matayoshi S., Jiang N., Katafuchi T., Koga K., Furue H., Yasaka T., Nakatsuka T., Zhou X.F., Kawasaki Y., Tanaka N., Yoshimura M. Actions of brain-derived neurotrophic factor on spinal nociceptive transmission during inflammation in the rat. J. Physiol. 2005, 569:685-695.
110. McTigue D.M., Horner P.J., Stokes B.T., Gage F.H. 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.
111. Mendell L.M., Munson J.B., Arvanian V.L. Neurotrophins and synaptic plasticity in the mammalian spinal cord. J. Physiol. 2001, 533:91-97.
112. Menei P., Montero-Menei C., Whittemore S.R., Bunge R.P., Bunge M.B. 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.
113. Merighi A., Carmignoto G., Gobbo S., Lossi L., Salio C., Vergnano A.M., Zonta M. Neurotrophins in spinal cord nociceptive pathways. Prog. Brain Res. 2004, 146:291-321.
114. Merighi A., Salio C., Ghirri A., Lossi L., Ferrini F., Betelli C., Bardoni R. BDNF as a pain modulator. Prog. Neurobiol. 2008, 85:297-317.
115. Minichiello L. TrkB signalling pathways in LTP and learning. Nat. Rev. Neurosci. 2009, 10:850-860.
116. Mizoguchi Y., Monji A., Kato T., Seki Y., Gotoh L., Horikawa H., Suzuki S.O., Iwaki T., Yonaha M., Hashioka S., Kanba S. Brain-derived neurotrophic factor induces sustained elevation of intracellular Ca2+ in rodent microglia. J. Immunol. 2009, 183:7778-7786.
117. Nagahara A.H., Tuszynski M.H. Potential therapeutic uses of BDNF in neurological and psychiatric disorders. Nat. Rev. Drug Discov. 2011, 10:209-219.
118. Nagappan G., Zaitsev E., Senatorov V.V., Yang J., Hempstead B.L., Lu B. Control of extracellular cleavage of ProBDNF by high frequency neuronal activity. Proc. Natl. Acad. Sci. U. S. A. 2009, 106:1267-1272.
119. Namiki J., Kojima A., Tator C.H. Effect of brain-derived neurotrophic factor, nerve growth factor, and neurotrophin-3 on functional recovery and regeneration after spinal cord injury in adult rats. J. Neurotrauma 2000, 17:1219-1231.
120. Nashmi R., Fehlings M.G. Mechanisms of axonal dysfunction after spinal cord injury: with an emphasis on the role of voltage-gated potassium channels. Brain Res. Brain Res. Rev. 2001, 38:165-191.
121. Novikov L., Novikova L., Kellerth J.O. Brain-derived neurotrophic factor promotes axonal regeneration and long-term survival of adult rat spinal motoneurons in vivo. Neuroscience 1997, 79:765-774.
122. Novikova L., Novikov L., Kellerth J.O. Effects of neurotransplants and BDNF on the survival and regeneration of injured adult spinal motoneurons. Eur. J. Neurosci. 1997, 9:2774-2777.
123. Novikova L.N., Novikov L.N., Kellerth J.O. BDNF abolishes the survival effect of NT-3 in axotomized Clarke neurons of adult rats. J. Comp. Neurol. 2000, 428:671-680.
124. Novikova L.N., Novikov L.N., Kellerth J.O. Survival effects of BDNF and NT-3 on axotomized rubrospinal neurons depend on the temporal pattern of neurotrophin administration. Eur. J. Neurosci. 2000, 12:776-780.
125. Onifer S.M., Smith G.M., Fouad K. Plasticity after spinal cord injury: relevance to recovery and approaches to facilitate it. Neurotherapeutics 2011, 8:283-293.
126. Oudega M., Hagg T. Neurotrophins promote regeneration of sensory axons in the adult rat spinal cord. Brain Res. 1999, 818:431-438.
127. Pezet S., Malcangio M., McMahon S.B. BDNF: a neuromodulator in nociceptive pathways?. Brain Res. Brain Res. Rev. 2002, 40:240-249.
128. Poo M.M. Neurotrophins as synaptic modulators. Nat. Rev. Neurosci. 2001, 2:24-32.
129. Rekling J.C., Funk G.D., Bayliss D.A., Dong X.W., Feldman J.L. Synaptic control of motoneuronal excitability. Physiol. Rev. 2000, 80:767-852.
130. Rivera C., Voipio J., Thomas-Crusells J., Li H., Emri Z., Sipila S., Payne J.A., Minichiello L., Saarma M., Kaila K. Mechanism of activity-dependent downregulation of the neuron-specific K-Cl cotransporter KCC2. J. Neurosci. 2004, 24:4683-4691.
131. Rose C.R., Blum R., Kafitz K.W., Kovalchuk Y., Konnerth A. From modulator to mediator: rapid effects of BDNF on ion channels. Bioessays 2004, 26:1185-1194.
132. Roux P.P., Barker P.A. Neurotrophin signalling through the p75 neurotrophin receptor. Prog. Neurobiol. 2002, 67:203-233.
133. Ruitenberg M.J., Plant G.W., Hamers F.P., Wortel J., Blits B., Dijkhuizen P.A., Gispen W.H., Boer G.J., Verhaagen J. 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.
134. Ruitenberg M.J., Blits B., Dijkhuizen P.A., te Beek E.T., Bakker A., van Heerikhuize J.J., Pool C.W., Hermens W.T., Boer G.J., Verhaagen J. 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.
135. Sasaki M., Radtke C., Tan A.M., Zhao P., Hamada H., Houkin K., Honmou O., Kocsis J.D. BDNF-hypersecreting human mesenchymal stem cells promote functional recovery, axonal sprouting, and protection of corticospinal neurons after spinal cord injury. J. Neurosci. 2009, 29:14932-14941.
136. Sharma H.S. Neurotrophic factors in combination: a possible new therapeutic strategy to influence pathophysiology of spinal cord injury and repair mechanisms. Curr. Pharm. Des. 2007, 13:1841-1874.
137. Sharma H.S. A select combination of neurotrophins enhances neuroprotection and functional recovery following spinal cord injury. Ann. N. Y. Acad. Sci. 2007, 1122:95-111.
138. Sharma H.S., Nyberg F., Westman J., Alm P., Gordh T., Lindholm D. Brain derived neurotrophic factor and insulin like growth factor-1 attenuate upregulation of nitric oxide synthase and cell injury following trauma to the spinal cord. An immunohistochemical study in the rat. Amino Acids 1998, 14:121-129.
139. Shumsky J.S., Tobias C.A., Tumolo M., Long W.D., Giszter S.F., Murray M. Delayed transplantation of fibroblasts genetically modified to secrete BDNF and NT-3 into a spinal cord injury site is associated with limited recovery of function. Exp. Neurol. 2003, 184:114-130.
140. Teng H.K., Teng K.K., Lee R., Wright S., Tevar S., Almeida R.D., Kermani P., Torkin R., Chen Z.Y., Lee F.S., Kraemer R.T., Nykjaer A., Hempstead B.L. ProBDNF induces neuronal apoptosis via activation of a receptor complex of p75NTR and sortilin. J. Neurosci. 2005, 25:5455-5463.
141. Tobias C.A., Shumsky J.S., Shibata M., Tuszynski M.H., Fischer I., Tessler A., Murray M. 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.
142. Ulmann L., Hatcher J.P., Hughes J.P., Chaumont S., Green P.J., Conquet F., Buell G.N., Reeve A.J., Chessell I.P., Rassendren F. Up-regulation of P2X4 receptors in spinal microglia after peripheral nerve injury mediates BDNF release and neuropathic pain. J. Neurosci. 2008, 28:11263-11268.
143. Vavrek R., Girgis J., Tetzlaff W., Hiebert G.W., Fouad K. BDNF promotes connections of corticospinal neurons onto spared descending interneurons in spinal cord injured rats. Brain 2006, 129:1534-1545.
144. Vavrek R., Pearse D.D., Fouad K. Neuronal populations capable of regeneration following a combined treatment in rats with spinal cord transection. J. Neurotrauma 2007, 24:1667-1673.
145. Vaynman S., Gomez-Pinilla F. License to run: exercise impacts functional plasticity in the intact and injured central nervous system by using neurotrophins. Neurorehabil. Neural Repair 2005, 19:283-295.
146. Wang K.C., Kim J.A., Sivasankaran R., Segal R., He Z. P75 interacts with the Nogo receptor as a co-receptor for Nogo, MAG and OMgp. Nature 2002, 420:74-78.
147. Weidner N., Ner A., Salimi N., Tuszynski M.H. Spontaneous corticospinal axonal plasticity and functional recovery after adult central nervous system injury. Proc. Natl. Acad. Sci. U. S. A. 2001, 98:3513-3518.
148. Wenjin W., Wenchao L., Hao Z., Feng L., Yan W., Wodong S., Xianqun F., Wenlong D. Electrical stimulation promotes BDNF expression in spinal cord neurons through Ca(2+)- and Erk-dependent signalling pathways. Cell. Mol. Neurobiol. 2011, 31:459-467.
149. Wilhelm J.C., Xu M., Cucoranu D., Chmielewski S., Holmes T., Lau K.S., Bassell G.J., English A.W. Cooperative roles of BDNF expression in neurons and Schwann cells are modulated by exercise to facilitate nerve regeneration. J. Neurosci. 2012, 32:5002-5009.
150. Wong S.T., Henley J.R., Kanning K.C., Huang K.H., Bothwell M., Poo M.M. A p75(NTR) and Nogo receptor complex mediates repulsive signalling by myelin-associated glycoprotein. Nat. Neurosci. 2002, 5:1302-1308.
151. Wong I., Liao H., Bai X., Zaknic A., Zhong J., Guan Y., Li H.Y., Wang Y.J., Zhou X.F. ProBDNF inhibits infiltration of ED1+ macrophages after spinal cord injury. Brain Behav. Immun. 2010, 24:585-597.
152. Xu X.M., Guenard V., Kleitman N., Aebischer P., Bunge M.B. 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.
153. Yamashita T., Tucker K.L., Barde Y.A. Neurotrophin binding to the p75 receptor modulates Rho activity and axonal outgrowth. Neuron 1999, 24:585-593.
154. Yan Q., Elliott J., Snider W.D. Brain-derived neurotrophic factor rescues spinal motor neurons from axotomy-induced cell death. Nature 1992, 360:753-755.
155. Yan Q., Rosenfeld R.D., Matheson C.R., Hawkins N., Lopez O.T., Bennett L., Welcher A.A. Expression of brain-derived neurotrophic factor protein in the adult rat central nervous system. Neuroscience 1997, 78:431-448.
156. Yang P., Yang Z. Enhancing intrinsic growth capacity promotes adult CNS regeneration. J. Neurol. Sci. 2012, 312:1-6.
157. 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.
158. Yick L.W., Wu W., So K.F., Yip H.K. Peripheral nerve graft and neurotrophic factors enhance neuronal survival and expression of nitric oxide synthase in Clarke's nucleus after hemisection of the spinal cord in adult rat. Exp. Neurol. 1999, 159:131-138.
159. Ying Z., Roy R.R., Edgerton V.R., Gomez-Pinilla F. Exercise restores levels of neurotrophins and synaptic plasticity following spinal cord injury. Exp. Neurol. 2005, 193:411-419.
160. Ying Z., Roy R.R., Zhong H., Zdunowski S., Edgerton V.R., Gomez-Pinilla F. BDNF-exercise interactions in the recovery of symmetrical stepping after a cervical hemisection in rats. Neuroscience 2008, 155:1070-1078.
161. Ying Z., Covalin A., Judy J., Gomez-Pinilla F. Hypothalamic stimulation enhances hippocampal BDNF plasticity in proportion to metabolic rate. Brain Stimul 2012, 5:642-646.
162. Zhang X., Xu Y., Wang J., Zhou Q., Pu S., Jiang W., Du D. The effect of intrathecal administration of glial activation inhibitors on dorsal horn BDNF overexpression and hind paw mechanical allodynia in spinal nerve ligated rats. J. Neural Transm. 2012, 119:329-336.
163. Zhou L., Shine H.D. Neurotrophic factors expressed in both cortex and spinal cord induce axonal plasticity after spinal cord injury. J. Neurosci. Res. 2003, 74:221-226.
164. Zhou X.F., Song X.Y., Zhong J.H., Barati S., Zhou F.H., Johnson S.M. Distribution and localization of pro-brain-derived neurotrophic factor-like immunoreactivity in the peripheral and central nervous system of the adult rat. J. Neurochem. 2004, 91:704-715.
165. Zhou L.J., Yang T., Wei X., Liu Y., Xin W.J., Chen Y., Pang R.P., Zang Y., Li Y.Y., Liu X.G. Brain-derived neurotrophic factor contributes to spinal long-term potentiation and mechanical hypersensitivity by activation of spinal microglia in rat. Brain Behav. Immun. 2011, 25:322-334.