Neurotrophin treatment to promote regeneration after traumatic CNS injury
Received date: 21 Mar 2013
Accepted date: 18 Jun 2013
Published date: 01 Oct 2013
Copyright
Neurotrophins are a family of growth factors that have been found to be central for the development and functional maintenance of the nervous system, participating in neurogenesis, neuronal survival, axonal growth, synaptogenesis and activity-dependent forms of synaptic plasticity. Trauma in the adult nervous system can disrupt the functional circuitry of neurons and result in severe functional deficits. The limitation of intrinsic growth capacity of adult nervous system and the presence of an inhospitable environment are the major hurdles for axonal regeneration of lesioned adult neurons. Neurotrophic factors have been shown to be excellent candidates in mediating neuronal repair and establishing functional circuitry via activating several growth signaling mechanisms including neuron-intrinsic regenerative programs. Here, we will review the effects of various neurotrophins in mediating recovery after injury to the adult spinal cord.
Key words: axonal guidance; neurotrophin; regeneration; functional recovery; sprouting
Lakshmi KELAMANGALATH , George M. SMITH . Neurotrophin treatment to promote regeneration after traumatic CNS injury[J]. Frontiers in Biology, 2013 , 8(5) : 486 -495 . DOI: 10.1007/s11515-013-1269-8
1 |
Bamber N I, Li H Y, Lu X B, Oudega M, Aebischer P, Xu X M (2001). Neurotrophins BDNF and NT-3 promote axonal re-entry into the distal host spinal cord through Schwann cell-seeded mini-channels. Eur J Neurosci, 13(2): 257–268
|
2 |
Bartus K, James N D, Bosch K D, Bradbury E J (2012). Chondroitin sulphate proteoglycans: key modulators of spinal cord and brain plasticity. Exp Neurol, 235(1): 5–17
|
3 |
Bibel M, Barde Y A (2000). Neurotrophins: key regulators of cell fate and cell shape in the vertebrate nervous system. Genes Dev, 14(23): 2919–2937
|
4 |
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(2): 190–201
|
5 |
Blum R, Konnerth A (2005). Neurotrophin-mediated rapid signaling in the central nervous system: mechanisms and functions. Physiology (Bethesda), 20(1): 70–78
|
6 |
Bonner J F, Blesch A, Neuhuber B, Fischer I (2010). Promoting directional axon growth from neural progenitors grafted into the injured spinal cord. J Neurosci Res, 88(6): 1182–1192
|
7 |
Boyd J G, Gordon T (2002). A dose-dependent facilitation and inhibition of peripheral nerve regeneration by brain-derived neurotrophic factor. Eur J Neurosci, 15(4): 613–626
|
8 |
Bretzner F, Liu J, Currie E, Roskams A J, Tetzlaff W (2008). Undesired effects of a combinatorial treatment for spinal cord injury—transplantation of olfactory ensheathing cells and BDNF infusion to the red nucleus. Eur J Neurosci, 28(9): 1795–1807
|
9 |
Brock J H, Rosenzweig E S, Blesch A, Moseanko R, Havton L A, Edgerton V R, Tuszynski M H (2010). Local and remote growth factor effects after primate spinal cord injury. J Neurosci, 30(29): 9728–9737
|
10 |
Cajal S R y 1928. Degeneration and regeneration of the nervous system. Hafner, New York
|
11 |
Cameron A A, Smith G M, Randall D C, Brown D R, Rabchevsky A G (2006). Genetic manipulation of intraspinal plasticity after spinal cord injury alters the severity of autonomic dysreflexia. J Neurosci, 26(11): 2923–2932
|
12 |
Cao Q, Xu X M, Devries W H, Enzmann G U, Ping P, Tsoulfas P, Wood P M, Bunge M B, Whittemore S R (2005). Functional recovery in traumatic spinal cord injury after transplantation of multineurotrophin-expressing glial-restricted precursor cells. J Neurosci, 25(30): 6947–6957
|
13 |
Chan J R, Cosgaya J M, Wu Y J, Shooter E M (2001). Neurotrophins are key mediators of the myelination program in the peripheral nervous system. Proc Natl Acad Sci USA, 98(25): 14661–14668
|
14 |
Chan J R, Watkins T A, Cosgaya J M, Zhang C Z, Chen L, Reichardt L F, Shooter E M, Barres B A (2004). NGF controls axonal receptivity to myelination by Schwann cells or oligodendrocytes. Neuron, 43(2): 183–191
|
15 |
Chao M V (2003a). Neurotrophins and their receptors: a convergence point for many signalling pathways. Nat Rev Neurosci, 4(4): 299–309
|
16 |
Chao M V (2003b). Neurotrophins and their receptors: a convergence point for many signalling pathways. Nat Rev Neurosci, 4(4): 299–309
|
17 |
Chiaretti A, Antonelli A, Genovese O, Pezzotti P, Rocco C D, Viola L, Riccardi R (2008). Nerve growth factor and doublecortin expression correlates with improved outcome in children with severe traumatic brain injury. J Trauma, 65(1): 80–85
|
18 |
Chu Q, Wang Y, Fu X, Zhang S (2004). Mechanism of in vitro differentiation of bone marrow stromal cells into neuron-like cells. J Huazhong Univ Sci Technolog Med Sci, 24(3): 259–261
|
19 |
Cosgaya J M, Chan J R, Shooter E M (2002). The neurotrophin receptor p75NTR as a positive modulator of myelination. Science, 298(5596): 1245–1248
|
20 |
Coumans J V, Lin T T, Dai H N, MacArthur L, McAtee M, Nash C, Bregman B S (2001). Axonal regeneration and functional recovery after complete spinal cord transection in rats by delayed treatment with transplants and neurotrophins. J Neurosci, 21(23): 9334–9344
|
21 |
Deumens R, Koopmans G C, Joosten E A (2005). Regeneration of descending axon tracts after spinal cord injury. Prog Neurobiol, 77(1-2): 57–89
|
22 |
Domeniconi M, Filbin M T (2005). Overcoming inhibitors in myelin to promote axonal regeneration. J Neurol Sci, 233(1-2): 43–47
|
23 |
Epa W R, Markovska K, Barrett G L (2004). The p75 neurotrophin receptor enhances TrkA signalling by binding to Shc and augmenting its phosphorylation. J Neurochem, 89(2): 344–353
|
24 |
Ferguson I A, Koide T, Rush R A (2001). Stimulation of corticospinal tract regeneration in the chronically injured spinal cord. Eur J Neurosci, 13(5): 1059–1064
|
25 |
Ferraro G B, Alabed Y Z, Fournier A E (2004). Molecular targets to promote central nervous system regeneration. Curr Neurovasc Res, 1(1): 61–75
|
26 |
Freidman W J (2010). Proneurotrophin, seizures, and neuronal apoptosis. Neuroscienctist, 16(3): 244–252
|
27 |
Galtrey C M, Kwok J C F, Carulli D, Rhodes K E, Fawcett J W (2008). Distribution and synthesis of extracellular matrix proteoglycans, hyaluronan, link proteins and tenascin-R in the rat spinal cord. Eur J Neurosci, 27(6): 1373–1390
|
28 |
Gámez E, Ikezaki K, Fukui M, Matsuda T (2003). Photoconstructs of nerve guidance prosthesis using photoreactive gelatin as a scaffold. Cell Transplant, 12(5): 481–490
|
29 |
Grill R J, Blesch A, Tuszynski M H (1997). Robust growth of chronically injured spinal cord axons induced by grafts of genetically modified NGF-secreting cells. Exp Neurol, 148(2): 444–452
|
30 |
Hendriks W T, Ruitenberg M J, Blits B, Boer G J, Verhaagen J (2004). Viral vector-mediated gene transfer of neurotrophins to promote regeneration of the injured spinal cord. Prog Brain Res, 146: 451–476
|
31 |
Höke A, Redett R, Hameed H, Jari R, Zhou C, Li Z B, Griffin J W, Brushart T M (2006). Schwann cells express motor and sensory phenotypes that regulate axon regeneration. J Neurosci, 26(38): 9646–9655
|
32 |
Hollis E R 2nd, Jamshidi P, Löw K, Blesch A, Tuszynski M H (2009). Induction of corticospinal regeneration by lentiviral trkB-induced Erk activation. Proc Natl Acad Sci USA, 106(17): 7215–7220
|
33 |
Hollis E R 2nd, Tuszynski M H (2011). Neurotrophins: potential therapeutic tools for the treatment of spinal cord injury. Neurotherapeutics, 8(4): 694–703
|
34 |
Huang E J, Reichardt L F (2003). Trk receptors: roles in neuronal signal transduction. Annu Rev Biochem, 72(1): 609–642
|
35 |
Iarikov D E, Kim B G, Dai H N, McAtee M, Kuhn P L, Bregman B S (2007). Delayed transplantation with exogenous neurotrophin administration enhances plasticity of corticofugal projections after spinal cord injury. J Neurotrauma, 24(4): 690–702
|
36 |
Ide C (1996). Peripheral nerve regeneration. Neurosci Res, 25(2): 101–121
|
37 |
Jin Y, Ziemba K S, Smith G M (2008). Axon growth across a lesion site along a preformed guidance pathway in the brain. Exp Neurol, 210(2): 521–530
|
38 |
Jones L L, Sajed D, Tuszynski M H (2003). Axonal regeneration through regions of chondroitin sulfate proteoglycan deposition after spinal cord injury: a balance of permissiveness and inhibition. J Neurosci, 23(28): 9276–9288
|
39 |
Kadoya K, Tsukada S, Lu P, Coppola G, Geschwind D, Filbin M T, Blesch A, Tuszynski M H (2009). Combined intrinsic and extrinsic neuronal mechanisms facilitate bridging axonal regeneration one year after spinal cord injury. Neuron, 64(2): 165–172
|
40 |
Kim G, Choe Y, Park J, Cho S, Kim K (2002). Activation of protein kinase A induces neuronal differentiation of HiB5 hippocampal progenitor cells. Brain Res Mol Brain Res, 109(1-2): 134–145
|
41 |
Kim J E, Liu B P, Park J H, Strittmatter S M (2004). Nogo-66 receptor prevents raphespinal and rubrospinal axon regeneration and limits functional recovery from spinal cord injury. Neuron, 44(3): 439–451
|
42 |
Kobayashi N R, Fan D P, Giehl K M, Bedard A M, Wiegand S J, 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(24): 9583–9595
|
43 |
Kuruvilla R, Zweifel L S, Glebova N O, Lonze B E, Valdez G, Ye H, Ginty D D (2004). A neurotrophin signaling cascade coordinates sympathetic neuron development through differential control of TrkA trafficking and retrograde signaling. Cell, 118(2): 243–255
|
44 |
Kusano K, Enomoto M, Hirai T, Tsoulfas P, Sotome S, Shinomiya K, Okawa A (2010). Transplanted neural progenitor cells expressing mutant NT3 promote myelination and partial hindlimb recovery in the chronic phase after spinal cord injury. Biochem Biophys Res Commun, 393(4): 812–817
|
45 |
Kwon B K, Liu J, Lam C, Plunet W, Oschipok L W, 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(11): 1164–1173
|
46 |
Kwon B K, Liu J, Messerer C, Kobayashi N R, 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(5): 3246–3251
|
47 |
Lee H, McKeon R J, Bellamkonda R V (2010). Sustained delivery of thermostabilized chABC enhances axonal sprouting and functional recovery after spinal cord injury. Proc Natl Acad Sci USA, 107(8): 3340–3345
|
48 |
Lehmann H C, Höke A (2010). Schwann cells as a therapeutic target for peripheral neuropathies. CNS Neurol Disord Drug Targets, 9(6): 801–806
|
49 |
Lessmann V, Gottmann K, Malcangio M (2003). Neurotrophin secretion: current facts and future prospects. Prog Neurobiol, 69(5): 341–374
|
50 |
Longhi L, Watson D J, Saatman K E, Thompson H J, Zhang C, Fujimoto S, Royo N, Castelbuono D, Raghupathi R, Trojanowski J Q, Lee V M, Wolfe J H, Stocchetti N, McIntosh T K (2004a). Ex vivo gene therapy using targeted engraftment of NGF-expressing human NT2N neurons attenuates cognitive deficits following traumatic brain injury in mice. J Neurotrauma, 21(12): 1723–1736
|
51 |
Longhi L, Watson D J, Saatman K E, Thompson H J, Zhang C, Fujimoto S, Royo N, Castelbuono D, Raghupathi R, Trojanowski J Q, Lee V M, Wolfe J H, Stocchetti N, McIntosh T K (2004b). Ex vivo gene therapy using targeted engraftment of NGF-expressing human NT2N neurons attenuates cognitive deficits following traumatic brain injury in mice. J Neurotrauma, 21(12): 1723–1736
|
52 |
Lopatina T, Kalinina N, Karagyaur M, Stambolsky D, Rubina K, Revischin A, Pavlova G, Parfyonova Y, Tkachuk V (2011). Adipose-derived stem cells stimulate regeneration of peripheral nerves: BDNF secreted by these cells promotes nerve healing and axon growth de novo. PLoS ONE, 6(3): e17899
|
53 |
Lu B, Pang P T, Woo N H (2005). The yin and yang of neurotrophin action. Nat Rev Neurosci, 6(8): 603–614
|
54 |
Lu P, Blesch A, Tuszynski M H (2001). Neurotrophism without neurotropism: BDNF promotes survival but not growth of lesioned corticospinal neurons. J Comp Neurol, 436(4): 456–470
|
55 |
Lu P, Jones L L, Snyder E Y, Tuszynski M H (2003). Neural stem cells constitutively secrete neurotrophic factors and promote extensive host axonal growth after spinal cord injury. Exp Neurol, 181(2): 115–129
|
56 |
Mahmood A, Lu D, Wang L, Chopp M (2002). Intracerebral transplantation of marrow stromal cells cultured with neurotrophic factors promotes functional recovery in adult rats subjected to traumatic brain injury. J Neurotrauma, 19(12): 1609–1617
|
57 |
Massey J M, Amps J, Viapiano M S, Matthews R T, Wagoner M R, Whitaker C M, Alilain W, Yonkof A L, Khalyfa A, Cooper N G F, Silver J, Onifer S M (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(2): 426–445
|
58 |
Nielson J L, Strong M K, Steward O (2011). A reassessment of whether cortical motor neurons die following spinal cord injury. J Comp Neurol, 519(14): 2852–2869
|
59 |
Novikova L N, Novikov L N, Kellerth J O (2000). Survival effects of BDNF and NT-3 on axotomized rubrospinal neurons depend on the temporal pattern of neurotrophin administration. Eur J Neurosci, 12(2): 776–780
|
60 |
Philips M F, Mattiasson G, Wieloch T, Björklund A, Johansson B B, Tomasevic G, Martínez-Serrano A, Lenzlinger P M, Sinson G, Grady M S, McIntosh T K (2001). Neuroprotective and behavioral efficacy of nerve growth factor-transfected hippocampal progenitor cell transplants after experimental traumatic brain injury. J Neurosurg, 94(5): 765–774
|
61 |
Ramer M S, Priestley J V, McMahon S B (2000). Functional regeneration of sensory axons into the adult spinal cord. Nature, 403(6767): 312–316
|
62 |
Ray S K, Dixon C E, Banik N L (2002). Molecular mechanisms in the pathogenesis of traumatic brain injury. Histol Histopathol, 17(4): 1137–1152
|
63 |
Romero M I, Rangappa N, Garry M G, Smith G M (2001). Functional regeneration of chronically injured sensory afferents into adult spinal cord after neurotrophin gene therapy. J Neurosci, 21(21): 8408–8416
|
64 |
Romero M I, Smith G M (1998). Adenoviral gene transfer into the normal and injured spinal cord: enhanced transgene stability by combined administration of temperature-sensitive virus and transient immune blockade. Gene Ther, 5(12): 1612–1621
|
65 |
Royo N C, Schouten J W, Fulp C T, Shimizu S, Marklund N, Graham D I, McIntosh T K (2003). From cell death to neuronal regeneration: building a new brain after traumatic brain injury. J Neuropathol Exp Neurol, 62(8): 801–811
|
66 |
Sinson G, Voddi M, McIntosh T K (1996). Combined fetal neural transplantation and nerve growth factor infusion: effects on neurological outcome following fluid-percussion brain injury in the rat. J Neurosurg, 84(4): 655–662
|
67 |
Smith GMandOnifer S (2011) Construction of pathways to promote axon growth within the adult central nervous system. Brain Research Bulletin Brain Res Bull. 2011 84(4–5).
|
68 |
Smith G M, Romero M I (1999). Adenoviral-mediated gene transfer to enhance neuronal survival, growth, and regeneration. J Neurosci Res, 55(2): 147–157
|
69 |
Tang X Q, Cai J, Nelson K D, Peng X J, Smith G M (2004a). Functional repair after dorsal root rhizotomy using nerve conduits and neurotrophic molecules. Eur J Neurosci, 20(5): 1211–1218
|
70 |
Tang X Q, Tanelian D L, Smith G M (2004b). Semaphorin3A inhibits nerve growth factor-induced sprouting of nociceptive afferents in adult rat spinal cord. J Neurosci, 24(4): 819–827
|
71 |
Taylor S J, Rosenzweig E S, McDonald J W 3rd, Sakiyama-Elbert S E (2006). Delivery of neurotrophin-3 from fibrin enhances neuronal fiber sprouting after spinal cord injury. J Control Release, 113(3): 226–235
|
72 |
Tobias C A, Shumsky J S, Shibata M, Tuszynski M H, Fischer I, Tessler A, Murray M (2003). 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, 184(1): 97–113
|
73 |
Tonra J R, Curtis R, Wong V, Cliffer K D, Park J S, Timmes A, Nguyen T, Lindsay R M, Acheson A, DiStefano P S (1998). Axotomy upregulates the anterograde transport and expression of brain-derived neurotrophic factor by sensory neurons. J Neurosci, 18(11): 4374–4383
|
74 |
Trojanowski J Q, Kleppner S R, Hartley R S, Miyazono M, Fraser N W, Kesari S, Lee V M (1997). Transfectable and transplantable postmitotic human neurons: a potential “platform” for gene therapy of nervous system diseases. Exp Neurol, 144(1): 92–97
|
75 |
Tuszynski M H, Gabriel K, Gage F H, 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(1): 157–173
|
76 |
Vavrek R, Girgis J, Tetzlaff W, Hiebert G W, Fouad K (2006). BDNF promotes connections of corticospinal neurons onto spared descending interneurons in spinal cord injured rats. Brain, 129(Pt 6): 1534–1545
|
77 |
Wang Z T, Yao W F, Deng Q J, Zhang X H, Zhang J N (2013). Protective effects of BDNF overexpression bone marrow stromal cell transplantation in rat models of traumatic brain injury. J Mol Neurosci, 49(2): 409–416
|
78 |
Woolley A G, Tait K J, Hurren B J, Fisher L, Sheard P W, Duxson M J (2008). Developmental loss of NT-3 in vivo results in reduced levels of myelin-specific proteins, a reduced extent of myelination and increased apoptosis of Schwann cells. Glia, 56(3): 306–317
|
79 |
Xiao J, Wong A, Kilpatrick T, Murray S (2010). BDNF ENHANCES CENTRAL NERVOUS SYSTEM MYELINATION VIA A DIRECT SIGNALLING TO OLIGODENDROGLIAL TrKB RECEPTORS. J Neurochem, 115: 36–36
|
80 |
Xiao J H, Kilpatrick T J, Murray S S (2009). The role of neurotrophins in the regulation of myelin development. Neurosignals, 17(4): 265–276
|
81 |
Xu X M, Guénard V, Kleitman N, Aebischer P, Bunge M B (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(2): 261–272
|
82 |
Ye J H, Houle J D (1997). Treatment of the chronically injured spinal cord with neurotrophic factors can promote axonal regeneration from supraspinal neurons. Exp Neurol, 143(1): 70–81
|
83 |
Zhou X F, Li W P, Zhou F H, Zhong J H, Mi J X, Wu L L, Xian C J (2005). Differential effects of endogenous brain-derived neurotrophic factor on the survival of axotomized sensory neurons in dorsal root ganglia: a possible role for the p75 neurotrophin receptor. Neuroscience, 132(3): 591–603
|
84 |
Zhou Z, Chen H, Zhang K, Yang H, Liu J, Huang Q (2003). Protective effect of nerve growth factor on neurons after traumatic brain injury. J Basic Clin Physiol Pharmacol, 14(3): 217–224
|
85 |
Zou L L, Huang L, Hayes R L, Black C, Qiu Y H, Perez-Polo J R, Le W, Clifton G L, Yang K (1999). Liposome-mediated NGF gene transfection following neuronal injury: potential therapeutic applications. Gene Ther, 6(6): 994–1005
|
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