Peripheral nerve regeneration and neurotrophic factors.
PDF (204K)
Journal: 1999/May - Journal of Anatomy
ISSN: 0021-8782
PUBMED: 10227662
Abstract:
The role of neurotrophic factors in the maintenance and survival of peripheral neuronal cells has been the subject of numerous studies. Administration of exogenous neurotrophic factors after nerve injury has been shown to mimic the effect of target organ-derived trophic factors on neuronal cells. After axotomy and during peripheral nerve regeneration, the neurotrophins NGF, NT-3 and BDNF show a well defined and selective beneficial effect on the survival and phenotypic expression of primary sensory neurons in dorsal root ganglia and of motoneurons in spinal cord. Other neurotrophic factors such as CNTF, GDNF and LIF also exert a variety of actions on neuronal cells, which appear to overlap and complement those of the neurotrophins. In addition, there is an indirect contribution of GGF to nerve regeneration. GGF is produced by neurons and stimulates proliferation of Schwann cells, underlining the close interaction between neuronal and glial cells during peripheral nerve regeneration. Different possibilities have been investigated for the delivery of growth factors to the injured neurons, in search of a suitable system for clinical applications. The studies reviewed in this article show the therapeutic potential of neurotrophic factors for the treatment of peripheral nerve injury and for neuropathies.
Open in
PUBMED | PMC | Google Scholar | Wikipedia
Relations:
Content
Citations
(102)
References
(209)
Diseases
(1)
Chemicals
(1)
Organisms
(2)
Processes
(1)
Anatomy
(4)
Similar articles
Articles by the same authors
Discussion board
J Anat 194(Pt 1): 1-14
PMID: 10227662

Peripheral nerve regeneration and neurotrophic factors

Abstract

The role of neurotrophic factors in the maintenance and survival of peripheral neuronal cells has been the subject of numerous studies. Administration of exogenous neurotrophic factors after nerve injury has been shown to mimic the effect of target organ-derived trophic factors on neuronal cells. After axotomy and during peripheral nerve regeneration, the neurotrophins NGF, NT-3 and BDNF show a well defined and selective beneficial effect on the survival and phenotypic expression of primary sensory neurons in dorsal root ganglia and of motoneurons in spinal cord. Other neurotrophic factors such as CNTF, GDNF and LIF also exert a variety of actions on neuronal cells, which appear to overlap and complement those of the neurotrophins. In addition, there is an indirect contribution of GGF to nerve regeneration. GGF is produced by neurons and stimulates proliferation of Schwann cells, underlining the close interaction between neuronal and glial cells during peripheral nerve regeneration. Different possibilities have been investigated for the delivery of growth factors to the injured neurons, in search of a suitable system for clinical applications. The studies reviewed in this article show the therapeutic potential of neurotrophic factors for the treatment of peripheral nerve injury and for neuropathies.

Keywords: Nerve injury, peripheral neuropathy

Full Text

The Full Text of this article is available as a PDF (204K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Acheson A, Barker PA, Alderson RF, Miller FD, Murphy RA. Detection of brain-derived neurotrophic factor-like activity in fibroblasts and Schwann cells: inhibition by antibodies to NGF. Neuron. 1991 Aug;7(2):265–275. [PubMed] [Google Scholar]
  • Acheson A, Conover JC, Fandl JP, DeChiara TM, Russell M, Thadani A, Squinto SP, Yancopoulos GD, Lindsay RM. A BDNF autocrine loop in adult sensory neurons prevents cell death. Nature. 1995 Mar 30;374(6521):450–453. [PubMed] [Google Scholar]
  • Adler R. Ciliary neurotrophic factor as an injury factor. Curr Opin Neurobiol. 1993 Oct;3(5):785–789. [PubMed] [Google Scholar]
  • Airaksinen MS, Koltzenburg M, Lewin GR, Masu Y, Helbig C, Wolf E, Brem G, Toyka KV, Thoenen H, Meyer M. Specific subtypes of cutaneous mechanoreceptors require neurotrophin-3 following peripheral target innervation. Neuron. 1996 Feb;16(2):287–295. [PubMed] [Google Scholar]
  • Anand P. Neurotrophins and peripheral neuropathy. Philos Trans R Soc Lond B Biol Sci. 1996 Mar 29;351(1338):449–454. [PubMed] [Google Scholar]
  • Anand P, Terenghi G, Warner G, Kopelman P, Williams-Chestnut RE, Sinicropi DV. The role of endogenous nerve growth factor in human diabetic neuropathy. Nat Med. 1996 Jun;2(6):703–707. [PubMed] [Google Scholar]
  • Anand P, Terenghi G, Birch R, Wellmer A, Cedarbaum JM, Lindsay RM, Williams-Chestnut RE, Sinicropi DV. Endogenous NGF and CNTF levels in human peripheral nerve injury. Neuroreport. 1997 May 27;8(8):1935–1938. [PubMed] [Google Scholar]
  • Anton ES, Weskamp G, Reichardt LF, Matthew WD. Nerve growth factor and its low-affinity receptor promote Schwann cell migration. Proc Natl Acad Sci U S A. 1994 Mar 29;91(7):2795–2799.[PMC free article] [PubMed] [Google Scholar]
  • Arakawa Y, Sendtner M, Thoenen H. Survival effect of ciliary neurotrophic factor (CNTF) on chick embryonic motoneurons in culture: comparison with other neurotrophic factors and cytokines. J Neurosci. 1990 Nov;10(11):3507–3515.[PMC free article] [PubMed] [Google Scholar]
  • Arce V, Pollock RA, Philippe JM, Pennica D, Henderson CE, deLapeyrière O. Synergistic effects of schwann- and muscle-derived factors on motoneuron survival involve GDNF and cardiotrophin-1 (CT-1). J Neurosci. 1998 Feb 15;18(4):1440–1448.[PMC free article] [PubMed] [Google Scholar]
  • Arvidsson J, Ygge J, Grant G. Cell loss in lumbar dorsal root ganglia and transganglionic degeneration after sciatic nerve resection in the rat. Brain Res. 1986 May 14;373(1-2):15–21. [PubMed] [Google Scholar]
  • Baloh RH, Tansey MG, Golden JP, Creedon DJ, Heuckeroth RO, Keck CL, Zimonjic DB, Popescu NC, Johnson EM, Jr, Milbrandt J. TrnR2, a novel receptor that mediates neurturin and GDNF signaling through Ret. Neuron. 1997 May;18(5):793–802. [PubMed] [Google Scholar]
  • Bandtlow CE, Heumann R, Schwab ME, Thoenen H. Cellular localization of nerve growth factor synthesis by in situ hybridization. EMBO J. 1987 Apr;6(4):891–899.[PMC free article] [PubMed] [Google Scholar]
  • Barbacid M. The Trk family of neurotrophin receptors. J Neurobiol. 1994 Nov;25(11):1386–1403. [PubMed] [Google Scholar]
  • Barde YA. The nerve growth factor family. Prog Growth Factor Res. 1990;2(4):237–248. [PubMed] [Google Scholar]
  • Barde YA. Neurotrophic factors: an evolutionary perspective. J Neurobiol. 1994 Nov;25(11):1329–1333. [PubMed] [Google Scholar]
  • Barde YA, Lindsay RM, Monard D, Thoenen H. New factor released by cultured glioma cells supporting survival and growth of sensory neurones. Nature. 1978 Aug 24;274(5673):818–818. [PubMed] [Google Scholar]
  • Belliveau DJ, Krivko I, Kohn J, Lachance C, Pozniak C, Rusakov D, Kaplan D, Miller FD. NGF and neurotrophin-3 both activate TrkA on sympathetic neurons but differentially regulate survival and neuritogenesis. J Cell Biol. 1997 Jan 27;136(2):375–388.[PMC free article] [PubMed] [Google Scholar]
  • Bennett DL, Dmietrieva N, Priestley JV, Clary D, McMahon SB. trkA, CGRP and IB4 expression in retrogradely labelled cutaneous and visceral primary sensory neurones in the rat. Neurosci Lett. 1996 Mar 8;206(1):33–36. [PubMed] [Google Scholar]
  • Bennett DL, Michael GJ, Ramachandran N, Munson JB, Averill S, Yan Q, McMahon SB, Priestley JV. A distinct subgroup of small DRG cells express GDNF receptor components and GDNF is protective for these neurons after nerve injury. J Neurosci. 1998 Apr 15;18(8):3059–3072.[PMC free article] [PubMed] [Google Scholar]
  • Berkemeier LR, Winslow JW, Kaplan DR, Nikolics K, Goeddel DV, Rosenthal A. Neurotrophin-5: a novel neurotrophic factor that activates trk and trkB. Neuron. 1991 Nov;7(5):857–866. [PubMed] [Google Scholar]
  • Beuche W, Friede RL. The role of non-resident cells in Wallerian degeneration. J Neurocytol. 1984 Oct;13(5):767–796. [PubMed] [Google Scholar]
  • Bixby JL, Lilien J, Reichardt LF. Identification of the major proteins that promote neuronal process outgrowth on Schwann cells in vitro. J Cell Biol. 1988 Jul;107(1):353–361.[PMC free article] [PubMed] [Google Scholar]
  • Braun S, Croizat B, Lagrange MC, Warter JM, Poindron P. Neurotrophins increase motoneurons' ability to innervate skeletal muscle fibers in rat spinal cord--human muscle cocultures. J Neurol Sci. 1996 Mar;136(1-2):17–23. [PubMed] [Google Scholar]
  • Brushart TM. Preferential reinnervation of motor nerves by regenerating motor axons. J Neurosci. 1988 Mar;8(3):1026–1031.[PMC free article] [PubMed] [Google Scholar]
  • Brushart TM. Motor axons preferentially reinnervate motor pathways. J Neurosci. 1993 Jun;13(6):2730–2738.[PMC free article] [PubMed] [Google Scholar]
  • Brushart TM, Seiler WA., 4th Selective reinnervation of distal motor stumps by peripheral motor axons. Exp Neurol. 1987 Aug;97(2):289–300. [PubMed] [Google Scholar]
  • Buchman VL, Davies AM. Different neurotrophins are expressed and act in a developmental sequence to promote the survival of embryonic sensory neurons. Development. 1993 Jul;118(3):989–1001. [PubMed] [Google Scholar]
  • Buj-Bello A, Buchman VL, Horton A, Rosenthal A, Davies AM. GDNF is an age-specific survival factor for sensory and autonomic neurons. Neuron. 1995 Oct;15(4):821–828. [PubMed] [Google Scholar]
  • Carraway KL, 3rd, Burden SJ. Neuregulins and their receptors. Curr Opin Neurobiol. 1995 Oct;5(5):606–612. [PubMed] [Google Scholar]
  • Carroll SL, Miller ML, Frohnert PW, Kim SS, Corbett JA. Expression of neuregulins and their putative receptors, ErbB2 and ErbB3, is induced during Wallerian degeneration. J Neurosci. 1997 Mar 1;17(5):1642–1659.[PMC free article] [PubMed] [Google Scholar]
  • Chao MV, Bothwell MA, Ross AH, Koprowski H, Lanahan AA, Buck CR, Sehgal A. Gene transfer and molecular cloning of the human NGF receptor. Science. 1986 Apr 25;232(4749):518–521. [PubMed] [Google Scholar]
  • Chao MV, Hempstead BL. p75 and Trk: a two-receptor system. Trends Neurosci. 1995 Jul;18(7):321–326. [PubMed] [Google Scholar]
  • Chen MS, Bermingham-McDonogh O, Danehy FT, Jr, Nolan C, Scherer SS, Lucas J, Gwynne D, Marchionni MA. Expression of multiple neuregulin transcripts in postnatal rat brains. J Comp Neurol. 1994 Nov 15;349(3):389–400. [PubMed] [Google Scholar]
  • Cho HJ, Kim SY, Park MJ, Kim DS, Kim JK, Chu MY. Expression of mRNA for brain-derived neurotrophic factor in the dorsal root ganglion following peripheral inflammation. Brain Res. 1997 Feb 28;749(2):358–362. [PubMed] [Google Scholar]
  • He C, Chen Z, Chen Z. Enhancement of motor nerve regeneration by nerve growth factor. Microsurgery. 1992;13(3):151–154. [PubMed] [Google Scholar]
  • Corness J, Shi TJ, Xu ZQ, Brulet P, Hökfelt T. Influence of leukemia inhibitory factor on galanin/GMAP and neuropeptide Y expression in mouse primary sensory neurons after axotomy. Exp Brain Res. 1996 Nov;112(1):79–88. [PubMed] [Google Scholar]
  • Curtis R, Adryan KM, Zhu Y, Harkness PJ, Lindsay RM, DiStefano PS. Retrograde axonal transport of ciliary neurotrophic factor is increased by peripheral nerve injury. Nature. 1993 Sep 16;365(6443):253–255. [PubMed] [Google Scholar]
  • Curtis R, Scherer SS, Somogyi R, Adryan KM, Ip NY, Zhu Y, Lindsay RM, DiStefano PS. Retrograde axonal transport of LIF is increased by peripheral nerve injury: correlation with increased LIF expression in distal nerve. Neuron. 1994 Jan;12(1):191–204. [PubMed] [Google Scholar]
  • Davis S, Aldrich TH, Valenzuela DM, Wong VV, Furth ME, Squinto SP, Yancopoulos GD. The receptor for ciliary neurotrophic factor. Science. 1991 Jul 5;253(5015):59–63. [PubMed] [Google Scholar]
  • Davies AM. The neurotrophic hypothesis: where does it stand? Philos Trans R Soc Lond B Biol Sci. 1996 Mar 29;351(1338):389–394. [PubMed] [Google Scholar]
  • Davies AM, Bandtlow C, Heumann R, Korsching S, Rohrer H, Thoenen H. Timing and site of nerve growth factor synthesis in developing skin in relation to innervation and expression of the receptor. Nature. 326(6111):353–358. [PubMed] [Google Scholar]
  • Davies AM, Minichiello L, Klein R. Developmental changes in NT3 signalling via TrkA and TrkB in embryonic neurons. EMBO J. 1995 Sep 15;14(18):4482–4489.[PMC free article] [PubMed] [Google Scholar]
  • Derby A, Engleman VW, Frierdich GE, Neises G, Rapp SR, Roufa DG. Nerve growth factor facilitates regeneration across nerve gaps: morphological and behavioral studies in rat sciatic nerve. Exp Neurol. 1993 Feb;119(2):176–191. [PubMed] [Google Scholar]
  • Diamond J, Holmes M, Coughlin M. Endogenous NGF and nerve impulses regulate the collateral sprouting of sensory axons in the skin of the adult rat. J Neurosci. 1992 Apr;12(4):1454–1466.[PMC free article] [PubMed] [Google Scholar]
  • Diamond J, Foerster A, Holmes M, Coughlin M. Sensory nerves in adult rats regenerate and restore sensory function to the skin independently of endogenous NGF. J Neurosci. 1992 Apr;12(4):1467–1476.[PMC free article] [PubMed] [Google Scholar]
  • DiStefano PS, Friedman B, Radziejewski C, Alexander C, Boland P, Schick CM, Lindsay RM, Wiegand SJ. The neurotrophins BDNF, NT-3, and NGF display distinct patterns of retrograde axonal transport in peripheral and central neurons. Neuron. 1992 May;8(5):983–993. [PubMed] [Google Scholar]
  • Dong Z, Brennan A, Liu N, Yarden Y, Lefkowitz G, Mirsky R, Jessen KR. Neu differentiation factor is a neuron-glia signal and regulates survival, proliferation, and maturation of rat Schwann cell precursors. Neuron. 1995 Sep;15(3):585–596. [PubMed] [Google Scholar]
  • Edström A, Ekström PA, Tonge D. Axonal outgrowth and neuronal apoptosis in cultured adult mouse dorsal root ganglion preparations: effects of neurotrophins, of inhibition of neurotrophin actions and of prior axotomy. Neuroscience. 1996 Dec;75(4):1165–1174. [PubMed] [Google Scholar]
  • Emerich DF, Hammang JP, Baetge EE, Winn SR. Implantation of polymer-encapsulated human nerve growth factor-secreting fibroblasts attenuates the behavioral and neuropathological consequences of quinolinic acid injections into rodent striatum. Exp Neurol. 1994 Nov;130(1):141–150. [PubMed] [Google Scholar]
  • Emerich DF, Winn SR, Hantraye PM, Peschanski M, Chen EY, Chu Y, McDermott P, Baetge EE, Kordower JH. Protective effect of encapsulated cells producing neurotrophic factor CNTF in a monkey model of Huntington's disease. Nature. 1997 Mar 27;386(6623):395–399. [PubMed] [Google Scholar]
  • Eriksson NP, Lindsay RM, Aldskogius H. BDNF and NT-3 rescue sensory but not motoneurones following axotomy in the neonate. Neuroreport. 1994 Jul 21;5(12):1445–1448. [PubMed] [Google Scholar]
  • Ernfors P, Ibáez CF, Ebendal T, Olson L, Persson H. Molecular cloning and neurotrophic activities of a protein with structural similarities to nerve growth factor: developmental and topographical expression in the brain. Proc Natl Acad Sci U S A. 1990 Jul;87(14):5454–5458.[PMC free article] [PubMed] [Google Scholar]
  • Ernfors Patrik, Merlio Jean-Phillipe, Persson Håkan. Cells Expressing mRNA for Neurotrophins and their Receptors During Embryonic Rat Development. Eur J Neurosci. 1992 Oct;4(11):1140–1158. [PubMed] [Google Scholar]
  • Ernfors P, Rosario CM, Merlio JP, Grant G, Aldskogius H, Persson H. Expression of mRNAs for neurotrophin receptors in the dorsal root ganglion and spinal cord during development and following peripheral or central axotomy. Brain Res Mol Brain Res. 1993 Mar;17(3-4):217–226. [PubMed] [Google Scholar]
  • Ernfors P, Lee KF, Kucera J, Jaenisch R. Lack of neurotrophin-3 leads to deficiencies in the peripheral nervous system and loss of limb proprioceptive afferents. Cell. 1994 May 20;77(4):503–512. [PubMed] [Google Scholar]
  • Federoff HJ, Geschwind MD, Geller AI, Kessler JA. Expression of nerve growth factor in vivo from a defective herpes simplex virus 1 vector prevents effects of axotomy on sympathetic ganglia. Proc Natl Acad Sci U S A. 1992 Mar 1;89(5):1636–1640.[PMC free article] [PubMed] [Google Scholar]
  • Fitzgerald M, Wall PD, Goedert M, Emson PC. Nerve growth factor counteracts the neurophysiological and neurochemical effects of chronic sciatic nerve section. Brain Res. 1985 Apr 15;332(1):131–141. [PubMed] [Google Scholar]
  • Friedlander DR, Grumet M, Edelman GM. Nerve growth factor enhances expression of neuron-glia cell adhesion molecule in PC12 cells. J Cell Biol. 1986 Feb;102(2):413–419.[PMC free article] [PubMed] [Google Scholar]
  • Friedman B, Scherer SS, Rudge JS, Helgren M, Morrisey D, McClain J, Wang DY, Wiegand SJ, Furth ME, Lindsay RM, et al. Regulation of ciliary neurotrophic factor expression in myelin-related Schwann cells in vivo. Neuron. 1992 Aug;9(2):295–305. [PubMed] [Google Scholar]
  • Friedman B, Kleinfeld D, Ip NY, Verge VM, Moulton R, Boland P, Zlotchenko E, Lindsay RM, Liu L. BDNF and NT-4/5 exert neurotrophic influences on injured adult spinal motor neurons. J Neurosci. 1995 Feb;15(2):1044–1056.[PMC free article] [PubMed] [Google Scholar]
  • Funakoshi H, Frisén J, Barbany G, Timmusk T, Zachrisson O, Verge VM, Persson H. Differential expression of mRNAs for neurotrophins and their receptors after axotomy of the sciatic nerve. J Cell Biol. 1993 Oct;123(2):455–465.[PMC free article] [PubMed] [Google Scholar]
  • Gao WQ, Dybdal N, Shinsky N, Murnane A, Schmelzer C, Siegel M, Keller G, Hefti F, Phillips HS, Winslow JW. Neurotrophin-3 reverses experimental cisplatin-induced peripheral sensory neuropathy. Ann Neurol. 1995 Jul;38(1):30–37. [PubMed] [Google Scholar]
  • Gargano N, Levi A, Alema S. Modulation of nerve growth factor internalization by direct interaction between p75 and TrkA receptors. J Neurosci Res. 1997 Oct 1;50(1):1–12. [PubMed] [Google Scholar]
  • Glass DJ, Yancopoulos GD. The neurotrophins and their receptors. Trends Cell Biol. 1993 Aug;3(8):262–268. [PubMed] [Google Scholar]
  • Gold BG. Axonal regeneration of sensory nerves is delayed by continuous intrathecal infusion of nerve growth factor. Neuroscience. 1997 Feb;76(4):1153–1158. [PubMed] [Google Scholar]
  • Grant G, Arvidsson J, Robertson B, Ygge J. Transganglionic transport of horseradish peroxidase in primary sensory neurons. Neurosci Lett. 1979 Apr;12(1):23–28. [PubMed] [Google Scholar]
  • 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 Jul;3(7):765–770. [PubMed] [Google Scholar]
  • Griesbeck O, Parsadanian AS, Sendtner M, Thoenen H. Expression of neurotrophins in skeletal muscle: quantitative comparison and significance for motoneuron survival and maintenance of function. J Neurosci Res. 1995 Sep 1;42(1):21–33. [PubMed] [Google Scholar]
  • Groves MJ, Christopherson T, Giometto B, Scaravilli F. Axotomy-induced apoptosis in adult rat primary sensory neurons. J Neurocytol. 1997 Sep;26(9):615–624. [PubMed] [Google Scholar]
  • Gu X, Thomas PK, King RH. Chemotropism in nerve regeneration studied in tissue culture. J Anat. 1995 Feb;186(Pt 1):153–163.[PMC free article] [PubMed] [Google Scholar]
  • Hall SM. Regeneration in cellular and acellular autografts in the peripheral nervous system. Neuropathol Appl Neurobiol. 1986 Jan-Feb;12(1):27–46. [PubMed] [Google Scholar]
  • Hall S. Axonal regeneration through acellular muscle grafts. J Anat. 1997 Jan;190(Pt 1):57–71.[PMC free article] [PubMed] [Google Scholar]
  • Hallbök F, Ibáez CF, Persson H. Evolutionary studies of the nerve growth factor family reveal a novel member abundantly expressed in Xenopus ovary. Neuron. 1991 May;6(5):845–858. [PubMed] [Google Scholar]
  • Helgren ME, Squinto SP, Davis HL, Parry DJ, Boulton TG, Heck CS, Zhu Y, Yancopoulos GD, Lindsay RM, DiStefano PS. Trophic effect of ciliary neurotrophic factor on denervated skeletal muscle. Cell. 1994 Feb 11;76(3):493–504. [PubMed] [Google Scholar]
  • Helgren ME, Cliffer KD, Torrento K, Cavnor C, Curtis R, DiStefano PS, Wiegand SJ, Lindsay RM. Neurotrophin-3 administration attenuates deficits of pyridoxine-induced large-fiber sensory neuropathy. J Neurosci. 1997 Jan 1;17(1):372–382.[PMC free article] [PubMed] [Google Scholar]
  • Henderson CE, Phillips HS, Pollock RA, Davies AM, Lemeulle C, Armanini M, Simmons L, Moffet B, Vandlen RA, Simpson LC corrected to Simmons L, et al. GDNF: a potent survival factor for motoneurons present in peripheral nerve and muscle. Science. 1994 Nov 11;266(5187):1062–1064. [PubMed] [Google Scholar]
  • Heumann R, Korsching S, Bandtlow C, Thoenen H. Changes of nerve growth factor synthesis in nonneuronal cells in response to sciatic nerve transection. J Cell Biol. 1987 Jun;104(6):1623–1631.[PMC free article] [PubMed] [Google Scholar]
  • Himes BT, Tessler A. Death of some dorsal root ganglion neurons and plasticity of others following sciatic nerve section in adult and neonatal rats. J Comp Neurol. 1989 Jun 8;284(2):215–230. [PubMed] [Google Scholar]
  • Hiruma S, Shimizu T, Huruta T, Satou T, Hu J, Tanji K, Hashimoto S. Ciliary neurotrophic factor immunoreactivity in rat intramuscular nerve during reinnervation through a silicone tube after severing of the rat sciatic nerve. Exp Mol Pathol. 1997 Feb;64(1):23–30. [PubMed] [Google Scholar]
  • Hoffer B, Olson L. Treatment strategies for neurodegenerative diseases based on trophic factors and cell transplantation techniques. J Neural Transm Suppl. 1997;49:1–10. [PubMed] [Google Scholar]
  • Hökfelt T, Zhang X, Wiesenfeld-Hallin Z. Messenger plasticity in primary sensory neurons following axotomy and its functional implications. Trends Neurosci. 1994 Jan;17(1):22–30. [PubMed] [Google Scholar]
  • Hollowell JP, Villadiego A, Rich KM. Sciatic nerve regeneration across gaps within silicone chambers: long-term effects of NGF and consideration of axonal branching. Exp Neurol. 1990 Oct;110(1):45–51. [PubMed] [Google Scholar]
  • Hopkins SJ, Rothwell NJ. Cytokines and the nervous system. I: Expression and recognition. Trends Neurosci. 1995 Feb;18(2):83–88. [PubMed] [Google Scholar]
  • Hory-Lee F, Russell M, Lindsay RM, Frank E. Neurotrophin 3 supports the survival of developing muscle sensory neurons in culture. Proc Natl Acad Sci U S A. 1993 Apr 1;90(7):2613–2617.[PMC free article] [PubMed] [Google Scholar]
  • Ip NY, Yancopoulos GD. Ciliary neurotrophic factor and its receptor complex. Prog Growth Factor Res. 1992;4(2):139–155. [PubMed] [Google Scholar]
  • Ip NY, Nye SH, Boulton TG, Davis S, Taga T, Li Y, Birren SJ, Yasukawa K, Kishimoto T, Anderson DJ, et al. CNTF and LIF act on neuronal cells via shared signaling pathways that involve the IL-6 signal transducing receptor component gp130. Cell. 1992 Jun 26;69(7):1121–1132. [PubMed] [Google Scholar]
  • Tonra JR, Curtis R, Wong V, Cliffer KD, Park JS, Timmes A, Nguyen T, Lindsay RM, Acheson A, DiStefano PS. Axotomy upregulates the anterograde transport and expression of brain-derived neurotrophic factor by sensory neurons. J Neurosci. 1998 Jun 1;18(11):4374–4383.[PMC free article] [PubMed] [Google Scholar]
  • Jing S, Wen D, Yu Y, Holst PL, Luo Y, Fang M, Tamir R, Antonio L, Hu Z, Cupples R, et al. GDNF-induced activation of the ret protein tyrosine kinase is mediated by GDNFR-alpha, a novel receptor for GDNF. Cell. 1996 Jun 28;85(7):1113–1124. [PubMed] [Google Scholar]
  • Johnson EM, Jr, Yip HK. Central nervous system and peripheral nerve growth factor provide trophic support critical to mature sensory neuronal survival. Nature. 314(6013):751–752. [PubMed] [Google Scholar]
  • Kaplan DR, Hempstead BL, Martin-Zanca D, Chao MV, Parada LF. The trk proto-oncogene product: a signal transducing receptor for nerve growth factor. Science. 1991 Apr 26;252(5005):554–558. [PubMed] [Google Scholar]
  • Kashiba H, Senba E, Kawai Y, Ueda Y, Tohyama M. Axonal blockade induces the expression of vasoactive intestinal polypeptide and galanin in rat dorsal root ganglion neurons. Brain Res. 1992 Apr 10;577(1):19–28. [PubMed] [Google Scholar]
  • Kashiba H, Ueda Y, Ueyama T, Nemoto K, Senba E. Relationship between BDNF- and trk-expressing neurones in rat dorsal root ganglion: an analysis by in situ hybridization. Neuroreport. 1997 Mar 24;8(5):1229–1234. [PubMed] [Google Scholar]
  • Kerekes N, Landry M, Rydh-Rinder M, Hökfelt T. The effect of NGF, BDNF and bFGF on expression of galanin in cultured rat dorsal root ganglia. Brain Res. 1997 Apr 18;754(1-2):131–141. [PubMed] [Google Scholar]
  • Kim DH, Gutin PH, Noble LJ, Nathan D, Yu JS, Nockels RP. Treatment with genetically engineered fibroblasts producing NGF or BDNF can accelerate recovery from traumatic spinal cord injury in the adult rat. Neuroreport. 1996 Sep 2;7(13):2221–2225. [PubMed] [Google Scholar]
  • 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 Apr;144(2):273–286. [PubMed] [Google Scholar]
  • Klein R, Parada LF, Coulier F, Barbacid M. trkB, a novel tyrosine protein kinase receptor expressed during mouse neural development. EMBO J. 1989 Dec 1;8(12):3701–3709.[PMC free article] [PubMed] [Google Scholar]
  • Klein R, Lamballe F, Bryant S, Barbacid M. The trkB tyrosine protein kinase is a receptor for neurotrophin-4. Neuron. 1992 May;8(5):947–956. [PubMed] [Google Scholar]
  • Krekoski CA, Parhad IM, Clark AW. Attenuation and recovery of nerve growth factor receptor mRNA in dorsal root ganglion neurons following axotomy. J Neurosci Res. 1996 Jan 1;43(1):1–11. [PubMed] [Google Scholar]
  • Kurek JB, Bower JJ, Romanella M, Koentgen F, Murphy M, Austin L. The role of leukemia inhibitory factor in skeletal muscle regeneration. Muscle Nerve. 1997 Jul;20(7):815–822. [PubMed] [Google Scholar]
  • Lamballe F, Klein R, Barbacid M. trkC, a new member of the trk family of tyrosine protein kinases, is a receptor for neurotrophin-3. Cell. 1991 Sep 6;66(5):967–979. [PubMed] [Google Scholar]
  • Levi-Montalcini R. The nerve growth factor: thirty-five years later. EMBO J. 1987 May;6(5):1145–1154.[PMC free article] [PubMed] [Google Scholar]
  • Lewin GR, Barde YA. Physiology of the neurotrophins. Annu Rev Neurosci. 1996;19:289–317. [PubMed] [Google Scholar]
  • Lewin SL, Utley DS, Cheng ET, Verity AN, Terris DJ. Simultaneous treatment with BDNF and CNTF after peripheral nerve transection and repair enhances rate of functional recovery compared with BDNF treatment alone. Laryngoscope. 1997 Jul;107(7):992–999. [PubMed] [Google Scholar]
  • Li L, Wu W, Lin LF, Lei M, Oppenheim RW, Houenou LJ. Rescue of adult mouse motoneurons from injury-induced cell death by glial cell line-derived neurotrophic factor. Proc Natl Acad Sci U S A. 1995 Oct 10;92(21):9771–9775.[PMC free article] [PubMed] [Google Scholar]
  • Li H, Terenghi G, Hall SM. Effects of delayed re-innervation on the expression of c-erbB receptors by chronically denervated rat Schwann cells in vivo. Glia. 1997 Aug;20(4):333–347. [PubMed] [Google Scholar]
  • Lin LF, Doherty DH, Lile JD, Bektesh S, Collins F. GDNF: a glial cell line-derived neurotrophic factor for midbrain dopaminergic neurons. Science. 1993 May 21;260(5111):1130–1132. [PubMed] [Google Scholar]
  • Lindsay RM. Nerve growth factors (NGF, BDNF) enhance axonal regeneration but are not required for survival of adult sensory neurons. J Neurosci. 1988 Jul;8(7):2394–2405.[PMC free article] [PubMed] [Google Scholar]
  • Lindsay RM. Role of neurotrophins and trk receptors in the development and maintenance of sensory neurons: an overview. Philos Trans R Soc Lond B Biol Sci. 1996 Mar 29;351(1338):365–373. [PubMed] [Google Scholar]
  • Lindsay RM. Therapeutic potential of the neurotrophins and neurotrophin-CNTF combinations in peripheral neuropathies and motor neuron diseases. Ciba Found Symp. 1996;196:39–53. [PubMed] [Google Scholar]
  • Lindsay RM, Harmar AJ. Nerve growth factor regulates expression of neuropeptide genes in adult sensory neurons. Nature. 1989 Jan 26;337(6205):362–364. [PubMed] [Google Scholar]
  • Liss AG, af Ekenstam FW, Wiberg M. Cell loss in sensory ganglia after peripheral nerve injury. An anatomical tracer study using lectin-coupled horseradish peroxidase in cats. Scand J Plast Reconstr Surg Hand Surg. 1994 Sep;28(3):177–188. [PubMed] [Google Scholar]
  • Madison RD, Archibald SJ, Brushart TM. Reinnervation accuracy of the rat femoral nerve by motor and sensory neurons. J Neurosci. 1996 Sep 15;16(18):5698–5703.[PMC free article] [PubMed] [Google Scholar]
  • Mahanthappa NK, Anton ES, Matthew WD. Glial growth factor 2, a soluble neuregulin, directly increases Schwann cell motility and indirectly promotes neurite outgrowth. J Neurosci. 1996 Aug 1;16(15):4673–4683.[PMC free article] [PubMed] [Google Scholar]
  • Maisonpierre PC, Belluscio L, Friedman B, Alderson RF, Wiegand SJ, Furth ME, Lindsay RM, Yancopoulos GD. NT-3, BDNF, and NGF in the developing rat nervous system: parallel as well as reciprocal patterns of expression. Neuron. 1990 Oct;5(4):501–509. [PubMed] [Google Scholar]
  • Maness LM, Kastin AJ, Weber JT, Banks WA, Beckman BS, Zadina JE. The neurotrophins and their receptors: structure, function, and neuropathology. Neurosci Biobehav Rev. 1994 Spring;18(1):143–159. [PubMed] [Google Scholar]
  • Marchionni MA, Goodearl AD, Chen MS, Bermingham-McDonogh O, Kirk C, Hendricks M, Danehy F, Misumi D, Sudhalter J, Kobayashi K, et al. Glial growth factors are alternatively spliced erbB2 ligands expressed in the nervous system. Nature. 1993 Mar 25;362(6418):312–318. [PubMed] [Google Scholar]
  • Martini R, Schachner M, Brushart TM. The L2/HNK-1 carbohydrate is preferentially expressed by previously motor axon-associated Schwann cells in reinnervated peripheral nerves. J Neurosci. 1994 Nov;14(11 Pt 2):7180–7191.[PMC free article] [PubMed] [Google Scholar]
  • Marzella PL, Clark GM, Shepherd RK, Bartlett PF, Kilpatrick TJ. LIF potentiates the NT-3-mediated survival of spiral ganglia neurones in vitro. Neuroreport. 1997 May 6;8(7):1641–1644. [PubMed] [Google Scholar]
  • Matheson CR, Wang J, Collins FD, Yan Q. Long-term survival effects of GDNF on neonatal rat facial motoneurons after axotomy. Neuroreport. 1997 May 6;8(7):1739–1742. [PubMed] [Google Scholar]
  • Matsuoka I, Nakane A, Kurihara K. Induction of LIF-mRNA by TGF-beta 1 in Schwann cells. Brain Res. 1997 Nov 21;776(1-2):170–180. [PubMed] [Google Scholar]
  • McAllister AK, Katz LC, Lo DC. Opposing roles for endogenous BDNF and NT-3 in regulating cortical dendritic growth. Neuron. 1997 May;18(5):767–778. [PubMed] [Google Scholar]
  • McMahon SB. NGF as a mediator of inflammatory pain. Philos Trans R Soc Lond B Biol Sci. 1996 Mar 29;351(1338):431–440. [PubMed] [Google Scholar]
  • McMahon SB, Armanini MP, Ling LH, Phillips HS. Expression and coexpression of Trk receptors in subpopulations of adult primary sensory neurons projecting to identified peripheral targets. Neuron. 1994 May;12(5):1161–1171. [PubMed] [Google Scholar]
  • McMahon SB, Bennett DL, Priestley JV, Shelton DL. The biological effects of endogenous nerve growth factor on adult sensory neurons revealed by a trkA-IgG fusion molecule. Nat Med. 1995 Aug;1(8):774–780. [PubMed] [Google Scholar]
  • Mendell LM. Neurotrophins and sensory neurons: role in development, maintenance and injury. A thematic summary. Philos Trans R Soc Lond B Biol Sci. 1996 Mar 29;351(1338):463–467. [PubMed] [Google Scholar]
  • Meyer M, Matsuoka I, Wetmore C, Olson L, Thoenen H. 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. 1992 Oct;119(1):45–54.[PMC free article] [PubMed] [Google Scholar]
  • Michael GJ, Averill S, Nitkunan A, Rattray M, Bennett DL, Yan Q, Priestley JV. Nerve growth factor treatment increases brain-derived neurotrophic factor selectively in TrkA-expressing dorsal root ganglion cells and in their central terminations within the spinal cord. J Neurosci. 1997 Nov 1;17(21):8476–8490.[PMC free article] [PubMed] [Google Scholar]
  • Molliver DC, Wright DE, Leitner ML, Parsadanian AS, Doster K, Wen D, Yan Q, Snider WD. IB4-binding DRG neurons switch from NGF to GDNF dependence in early postnatal life. Neuron. 1997 Oct;19(4):849–861. [PubMed] [Google Scholar]
  • Mulderry PK. Neuropeptide expression by newborn and adult rat sensory neurons in culture: effects of nerve growth factor and other neurotrophic factors. Neuroscience. 1994 Apr;59(3):673–688. [PubMed] [Google Scholar]
  • Munson JB, McMahon SB. Effects of GDNF on axotomized sensory and motor neurons in adult rats. Eur J Neurosci. 1997 Jun;9(6):1126–1129. [PubMed] [Google Scholar]
  • Munson JB, Shelton DL, McMahon SB. Adult mammalian sensory and motor neurons: roles of endogenous neurotrophins and rescue by exogenous neurotrophins after axotomy. J Neurosci. 1997 Jan 1;17(1):470–476.[PMC free article] [PubMed] [Google Scholar]
  • Naveilhan P, ElShamy WM, Ernfors P. Differential regulation of mRNAs for GDNF and its receptors Ret and GDNFR alpha after sciatic nerve lesion in the mouse. Eur J Neurosci. 1997 Jul;9(7):1450–1460. [PubMed] [Google Scholar]
  • Nawa H, Yamamori T, Le T, Patterson PH. Generation of neuronal diversity: analogies and homologies with hematopoiesis. Cold Spring Harb Symp Quant Biol. 1990;55:247–253. [PubMed] [Google Scholar]
  • Newman JP, Verity AN, Hawatmeh S, Fee WE, Jr, Terris DJ. Ciliary neurotrophic factors enhances peripheral nerve regeneration. Arch Otolaryngol Head Neck Surg. 1996 Apr;122(4):399–403. [PubMed] [Google Scholar]
  • Novikov L, Novikova L, Kellerth JO. Brain-derived neurotrophic factor promotes survival and blocks nitric oxide synthase expression in adult rat spinal motoneurons after ventral root avulsion. Neurosci Lett. 1995 Nov 10;200(1):45–48. [PubMed] [Google Scholar]
  • Novikova L, Novikov L, Kellerth JO. Effects of neurotransplants and BDNF on the survival and regeneration of injured adult spinal motoneurons. Eur J Neurosci. 1997 Dec;9(12):2774–2777. [PubMed] [Google Scholar]
  • Nguyen QT, Parsadanian AS, Snider WD, Lichtman JW. Hyperinnervation of neuromuscular junctions caused by GDNF overexpression in muscle. Science. 1998 Mar 13;279(5357):1725–1729. [PubMed] [Google Scholar]
  • Oakley RA, Garner AS, Large TH, Frank E. Muscle sensory neurons require neurotrophin-3 from peripheral tissues during the period of normal cell death. Development. 1995 May;121(5):1341–1350. [PubMed] [Google Scholar]
  • Oakley RA, Lefcort FB, Clary DO, Reichardt LF, Prevette D, Oppenheim RW, Frank E. Neurotrophin-3 promotes the differentiation of muscle spindle afferents in the absence of peripheral targets. J Neurosci. 1997 Jun 1;17(11):4262–4274.[PMC free article] [PubMed] [Google Scholar]
  • Ohara S, Tantuwaya V, DiStefano PS, Schmidt RE. Exogenous NT-3 mitigates the transganglionic neuropeptide Y response to sciatic nerve injury. Brain Res. 1995 Nov 13;699(1):143–148. [PubMed] [Google Scholar]
  • Oppenheim RW. Cell death during development of the nervous system. Annu Rev Neurosci. 1991;14:453–501. [PubMed] [Google Scholar]
  • Perry VH, Brown MC, Gordon S. The macrophage response to central and peripheral nerve injury. A possible role for macrophages in regeneration. J Exp Med. 1987 Apr 1;165(4):1218–1223.[PMC free article] [PubMed] [Google Scholar]
  • Rath S, Green CJ. Selectivity of distal reinnervation of regenerating mixed motor and sensory nerve fibres across muscle grafts in rats. Br J Plast Surg. 1991 Apr;44(3):215–218. [PubMed] [Google Scholar]
  • Rende M, Muir D, Ruoslahti E, Hagg T, Varon S, Manthorpe M. Immunolocalization of ciliary neuronotrophic factor in adult rat sciatic nerve. Glia. 1992;5(1):25–32. [PubMed] [Google Scholar]
  • Rende M, Provenzano C, Tonali P. Modulation of low-affinity nerve growth factor receptor in injured adult rat spinal cord motoneurons. J Comp Neurol. 1993 Dec 22;338(4):560–574. [PubMed] [Google Scholar]
  • Rende M, Provenzano C, Stipa G, Tonali P. Effects of sciatic nerve grafts on choline acetyltransferase and p75 expression in transected adult hypoglossal motoneurons. Neuroscience. 1997 Nov;81(2):517–525. [PubMed] [Google Scholar]
  • Reynolds ML, Woolf CJ. Reciprocal Schwann cell-axon interactions. Curr Opin Neurobiol. 1993 Oct;3(5):683–693. [PubMed] [Google Scholar]
  • Rich KM, Yip HK, Osborne PA, Schmidt RE, Johnson EM., Jr Role of nerve growth factor in the adult dorsal root ganglia neuron and its response to injury. J Comp Neurol. 1984 Nov 20;230(1):110–118. [PubMed] [Google Scholar]
  • Rich KM, Alexander TD, Pryor JC, Hollowell JP. Nerve growth factor enhances regeneration through silicone chambers. Exp Neurol. 1989 Aug;105(2):162–170. [PubMed] [Google Scholar]
  • Rich KM, Disch SP, Eichler ME. The influence of regeneration and nerve growth factor on the neuronal cell body reaction to injury. J Neurocytol. 1989 Oct;18(5):569–576. [PubMed] [Google Scholar]
  • Richardson PM. Ciliary neurotrophic factor: a review. Pharmacol Ther. 1994 Aug;63(2):187–198. [PubMed] [Google Scholar]
  • Roberson MD, Toews AD, Bouldin TW, Weaver J, Goines ND, Morell P. NGFR-mRNA expression in sciatic nerve: a sensitive indicator of early stages of axonopathy. Brain Res Mol Brain Res. 1995 Feb;28(2):231–238. [PubMed] [Google Scholar]
  • Rodriguez-Tébar A, Dechant G, Barde YA. Binding of brain-derived neurotrophic factor to the nerve growth factor receptor. Neuron. 1990 Apr;4(4):487–492. [PubMed] [Google Scholar]
  • Rodríguez-Tébar A, Dechant G, Götz R, Barde YA. Binding of neurotrophin-3 to its neuronal receptors and interactions with nerve growth factor and brain-derived neurotrophic factor. EMBO J. 1992 Mar;11(3):917–922.[PMC free article] [PubMed] [Google Scholar]
  • Rothwell NJ, Hopkins SJ. Cytokines and the nervous system II: Actions and mechanisms of action. Trends Neurosci. 1995 Mar;18(3):130–136. [PubMed] [Google Scholar]
  • Rush RA, Mayo R, Zettler C. The regulation of nerve growth factor synthesis and delivery to peripheral neurons. Pharmacol Ther. 1995 Jan;65(1):93–123. [PubMed] [Google Scholar]
  • Rush RA, Chie E, Liu D, Tafreshi A, Zettler C, Zhou XF. Neurotrophic factors are required by mature sympathetic neurons for survival, transmission and connectivity. Clin Exp Pharmacol Physiol. 1997 Aug;24(8):549–555. [PubMed] [Google Scholar]
  • Rutishauser U. Adhesion molecules of the nervous system. Curr Opin Neurobiol. 1993 Oct;3(5):709–715. [PubMed] [Google Scholar]
  • Rydén M, Ibáez CF. Binding of neurotrophin-3 to p75LNGFR, TrkA, and TrkB mediated by a single functional epitope distinct from that recognized by trkC. J Biol Chem. 1996 Mar 8;271(10):5623–5627. [PubMed] [Google Scholar]
  • Sahenk Z, Seharaseyon J, Mendell JR. CNTF potentiates peripheral nerve regeneration. Brain Res. 1994 Aug 29;655(1-2):246–250. [PubMed] [Google Scholar]
  • Salzer JL, Bunge RP. Studies of Schwann cell proliferation. I. An analysis in tissue culture of proliferation during development, Wallerian degeneration, and direct injury. J Cell Biol. 1980 Mar;84(3):739–752.[PMC free article] [PubMed] [Google Scholar]
  • Salzer JL, Williams AK, Glaser L, Bunge RP. Studies of Schwann cell proliferation. II. Characterization of the stimulation and specificity of the response to a neurite membrane fraction. J Cell Biol. 1980 Mar;84(3):753–766.[PMC free article] [PubMed] [Google Scholar]
  • Schmalbruch H. Loss of sensory neurons after sciatic nerve section in the rat. Anat Rec. 1987 Nov;219(3):323–329. [PubMed] [Google Scholar]
  • Seilheimer B, Schachner M. Regulation of neural cell adhesion molecule expression on cultured mouse Schwann cells by nerve growth factor. EMBO J. 1987 Jun;6(6):1611–1616.[PMC free article] [PubMed] [Google Scholar]
  • Sendtner M, Kreutzberg GW, Thoenen H. Ciliary neurotrophic factor prevents the degeneration of motor neurons after axotomy. Nature. 1990 May 31;345(6274):440–441. [PubMed] [Google Scholar]
  • Sendtner M, Stöckli KA, Thoenen H. Synthesis and localization of ciliary neurotrophic factor in the sciatic nerve of the adult rat after lesion and during regeneration. J Cell Biol. 1992 Jul;118(1):139–148.[PMC free article] [PubMed] [Google Scholar]
  • Sendtner M, Götz R, Holtmann B, Thoenen H. Endogenous ciliary neurotrophic factor is a lesion factor for axotomized motoneurons in adult mice. J Neurosci. 1997 Sep 15;17(18):6999–7006.[PMC free article] [PubMed] [Google Scholar]
  • Son YJ, Thompson WJ. Schwann cell processes guide regeneration of peripheral axons. Neuron. 1995 Jan;14(1):125–132. [PubMed] [Google Scholar]
  • Springer JE, Seeburger JL, He J, Gabrea A, Blankenhorn EP, Bergman LW. cDNA sequence and differential mRNA regulation of two forms of glial cell line-derived neurotrophic factor in Schwann cells and rat skeletal muscle. Exp Neurol. 1995 Jan;131(1):47–52. [PubMed] [Google Scholar]
  • Squinto SP, Stitt TN, Aldrich TH, Davis S, Bianco SM, Radziejewski C, Glass DJ, Masiakowski P, Furth ME, Valenzuela DM, et al. trkB encodes a functional receptor for brain-derived neurotrophic factor and neurotrophin-3 but not nerve growth factor. Cell. 1991 May 31;65(5):885–893. [PubMed] [Google Scholar]
  • Sterne GD, Brown RA, Green CJ, Terenghi G. Neurotrophin-3 delivered locally via fibronectin mats enhances peripheral nerve regeneration. Eur J Neurosci. 1997 Jul;9(7):1388–1396. [PubMed] [Google Scholar]
  • Sterne GD, Coulton GR, Brown RA, Green CJ, Terenghi G. Neurotrophin-3-enhanced nerve regeneration selectively improves recovery of muscle fibers expressing myosin heavy chains 2b. J Cell Biol. 1997 Nov 3;139(3):709–715.[PMC free article] [PubMed] [Google Scholar]
  • Stöckli KA, Lottspeich F, Sendtner M, Masiakowski P, Carroll P, Götz R, Lindholm D, Thoenen H. Molecular cloning, expression and regional distribution of rat ciliary neurotrophic factor. Nature. 1989 Dec 21;342(6252):920–923. [PubMed] [Google Scholar]
  • Subang MC, Bisby MA, Richardson PM. Delay of CNTF decrease following peripheral nerve injury in C57BL/Wld mice. J Neurosci Res. 1997 Sep 1;49(5):563–568. [PubMed] [Google Scholar]
  • Sun Y, Landis SC, Zigmond RE. Signals triggering the induction of leukemia inhibitory factor in sympathetic superior cervical ganglia and their nerve trunks after axonal injury. Mol Cell Neurosci. 1996 Feb;7(2):152–163. [PubMed] [Google Scholar]
  • Sun Y, Zigmond RE. Leukaemia inhibitory factor induced in the sciatic nerve after axotomy is involved in the induction of galanin in sensory neurons. Eur J Neurosci. 1996 Oct;8(10):2213–2220. [PubMed] [Google Scholar]
  • Tessarollo L, Vogel KS, Palko ME, Reid SW, Parada LF. Targeted mutation in the neurotrophin-3 gene results in loss of muscle sensory neurons. Proc Natl Acad Sci U S A. 1994 Dec 6;91(25):11844–11848.[PMC free article] [PubMed] [Google Scholar]
  • Tham S, Dowsing B, Finkelstein D, Donato R, Cheema SS, Bartlett PF, Morrison WA. Leukemia inhibitory factor enhances the regeneration of transected rat sciatic nerve and the function of reinnervated muscle. J Neurosci Res. 1997 Jan 15;47(2):208–215. [PubMed] [Google Scholar]
  • Thoenen H, Barde YA. Physiology of nerve growth factor. Physiol Rev. 1980 Oct;60(4):1284–1335. [PubMed] [Google Scholar]
  • Thompson SW, Vernallis AB, Heath JK, Priestley JV. Leukaemia inhibitory factor is retrogradely transported by a distinct population of adult rat sensory neurons: co-localization with trkA and other neurochemical markers. Eur J Neurosci. 1997 Jun;9(6):1244–1251. [PubMed] [Google Scholar]
  • Trachtenberg JT, Thompson WJ. Schwann cell apoptosis at developing neuromuscular junctions is regulated by glial growth factor. Nature. 1996 Jan 11;379(6561):174–177. [PubMed] [Google Scholar]
  • Tuszynski MH, Peterson DA, Ray J, Baird A, Nakahara Y, Gage FH. Fibroblasts genetically modified to produce nerve growth factor induce robust neuritic ingrowth after grafting to the spinal cord. Exp Neurol. 1994 Mar;126(1):1–14. [PubMed] [Google Scholar]
  • Tuszynski MH, Gabriel K, Gage FH, Suhr S, Meyer S, Rosetti A. Nerve growth factor delivery by gene transfer induces differential outgrowth of sensory, motor, and noradrenergic neurites after adult spinal cord injury. Exp Neurol. 1996 Jan;137(1):157–173. [PubMed] [Google Scholar]
  • Ulenkate HJ, Kaal EC, Gispen WH, Jennekens FG. Ciliary neurotrophic factor improves muscle fibre reinnervation after facial nerve crush in young rats. Acta Neuropathol. 1994;88(6):558–564. [PubMed] [Google Scholar]
  • Utley DS, Lewin SL, Cheng ET, Verity AN, Sierra D, Terris DJ. Brain-derived neurotrophic factor and collagen tubulization enhance functional recovery after peripheral nerve transection and repair. Arch Otolaryngol Head Neck Surg. 1996 Apr;122(4):407–413. [PubMed] [Google Scholar]
  • Vejsada R, Sagot Y, Kato AC. BDNF-mediated rescue of axotomized motor neurones decreases with increasing dose. Neuroreport. 1994 Oct 3;5(15):1889–1892. [PubMed] [Google Scholar]
  • Vejsada R, Sagot Y, Kato AC. Quantitative comparison of the transient rescue effects of neurotrophic factors on axotomized motoneurons in vivo. Eur J Neurosci. 1995 Jan 1;7(1):108–115. [PubMed] [Google Scholar]
  • Verge VM, Merlio JP, Grondin J, Ernfors P, Persson H, Riopelle RJ, Hökfelt T, Richardson PM. Colocalization of NGF binding sites, trk mRNA, and low-affinity NGF receptor mRNA in primary sensory neurons: responses to injury and infusion of NGF. J Neurosci. 1992 Oct;12(10):4011–4022.[PMC free article] [PubMed] [Google Scholar]
  • Verge VM, Richardson PM, Wiesenfeld-Hallin Z, Hökfelt T. Differential influence of nerve growth factor on neuropeptide expression in vivo: a novel role in peptide suppression in adult sensory neurons. J Neurosci. 1995 Mar;15(3 Pt 1):2081–2096.[PMC free article] [PubMed] [Google Scholar]
  • Verge VM, Gratto KA, Karchewski LA, Richardson PM. Neurotrophins and nerve injury in the adult. Philos Trans R Soc Lond B Biol Sci. 1996 Mar 29;351(1338):423–430. [PubMed] [Google Scholar]
  • Verdi JM, Groves AK, Fariñas I, Jones K, Marchionni MA, Reichardt LF, Anderson DJ. A reciprocal cell-cell interaction mediated by NT-3 and neuregulins controls the early survival and development of sympathetic neuroblasts. Neuron. 1996 Mar;16(3):515–527.[PMC free article] [PubMed] [Google Scholar]
  • Wakisaka S, Takikita S, Youn SH, Kurisu K. Partial coexistence of neuropeptide Y and calbindin D28k in the trigeminal ganglion following peripheral axotomy of the inferior alveolar nerve in the rat. Brain Res. 1996 Jan 29;707(2):228–234. [PubMed] [Google Scholar]
  • Wang W, Salvaterra PM, Loera S, Chiu AY. Brain-derived neurotrophic factor spares choline acetyltransferase mRNA following axotomy of motor neurons in vivo. J Neurosci Res. 1997 Jan 15;47(2):134–143. [PubMed] [Google Scholar]
  • Whitworth IH, Terenghi G, Green CJ, Brown RA, Stevens E, Tomlinson DR. Targeted delivery of nerve growth factor via fibronectin conduits assists nerve regeneration in control and diabetic rats. Eur J Neurosci. 1995 Nov 1;7(11):2220–2225. [PubMed] [Google Scholar]
  • Whitworth IH, Brown RA, Doré CJ, Anand P, Green CJ, Terenghi G. Nerve growth factor enhances nerve regeneration through fibronectin grafts. J Hand Surg Br. 1996 Aug;21(4):514–522. [PubMed] [Google Scholar]
  • Wong BJ, Mattox DE. Experimental nerve regeneration. A review. Otolaryngol Clin North Am. 1991 Jun;24(3):739–752. [PubMed] [Google Scholar]
  • Wong J, Oblinger MM. NGF rescues substance P expression but not neurofilament or tubulin gene expression in axotomized sensory neurons. J Neurosci. 1991 Feb;11(2):543–552.[PMC free article] [PubMed] [Google Scholar]
  • Woolf CJ. Phenotypic modification of primary sensory neurons: the role of nerve growth factor in the production of persistent pain. Philos Trans R Soc Lond B Biol Sci. 1996 Mar 29;351(1338):441–448. [PubMed] [Google Scholar]
  • Wright DE, Snider WD. Neurotrophin receptor mRNA expression defines distinct populations of neurons in rat dorsal root ganglia. J Comp Neurol. 1995 Jan 16;351(3):329–338. [PubMed] [Google Scholar]
  • Yamamori T, Fukada K, Aebersold R, Korsching S, Fann MJ, Patterson PH. The cholinergic neuronal differentiation factor from heart cells is identical to leukemia inhibitory factor. Science. 1989 Dec 15;246(4936):1412–1416. [PubMed] [Google Scholar]
  • Yan Q, Elliott J, Snider WD. Brain-derived neurotrophic factor rescues spinal motor neurons from axotomy-induced cell death. Nature. 1992 Dec 24;360(6406):753–755. [PubMed] [Google Scholar]
  • Yan Q, Matheson C, Lopez OT. In vivo neurotrophic effects of GDNF on neonatal and adult facial motor neurons. Nature. 1995 Jan 26;373(6512):341–344. [PubMed] [Google Scholar]
  • You S, Petrov T, Chung PH, Gordon T. The expression of the low affinity nerve growth factor receptor in long-term denervated Schwann cells. Glia. 1997 Jun;20(2):87–100. [PubMed] [Google Scholar]
  • Zhang L, Schmidt RE, Yan Q, Snider WD. NGF and NT-3 have differing effects on the growth of dorsal root axons in developing mammalian spinal cord. J Neurosci. 1994 Sep;14(9):5187–5201.[PMC free article] [PubMed] [Google Scholar]
  • Zhang X, Ji RR, Nilsson S, Villar M, Ubink R, Ju G, Wiesenfeld-Hallin Z, Hökfelt T. Neuropeptide Y and galanin binding sites in rat and monkey lumbar dorsal root ganglia and spinal cord and effect of peripheral axotomy. Eur J Neurosci. 1995 Mar 1;7(3):367–380. [PubMed] [Google Scholar]
  • Zhou XF, Rush RA. Peripheral projections of rat primary sensory neurons immunoreactive for neurotrophin 3. J Comp Neurol. 1995 Dec 4;363(1):69–77. [PubMed] [Google Scholar]
  • Zhou XF, Rush RA. Endogenous brain-derived neurotrophic factor is anterogradely transported in primary sensory neurons. Neuroscience. 1996 Oct;74(4):945–953. [PubMed] [Google Scholar]
  • Zhou XF, Chie ET, Deng YS, Rush RA. Rat mature sympathetic neurones derive neurotrophin 3 from peripheral effector tissues. Eur J Neurosci. 1997 Dec;9(12):2753–2764. [PubMed] [Google Scholar]
Blond McIndoe Centre, Queen Victoria Hospital, East Grinstead, Sussex, UK
Correspondence to Dr G. Terenghi, Blond McIndoe Laboratories, Department of Surgery, Royal Free and University College Medical School, Rowland Hill Street, London NW3 2QG, UK. Tel.: +44 0171 794 0500, ext. 3944; e-mail: ku.oc.nomed.lcu.eodnicm@ihgneret
Copyright © 1999 Anatomical Society of Great Britain and Ireland

Abstract

The role of neurotrophic factors in the maintenance and survival of peripheral neuronal cells has been the subject of numerous studies. Administration of exogenous neurotrophic factors after nerve injury has been shown to mimic the effect of target organ-derived trophic factors on neuronal cells. After axotomy and during peripheral nerve regeneration, the neurotrophins NGF, NT-3 and BDNF show a well defined and selective beneficial effect on the survival and phenotypic expression of primary sensory neurons in dorsal root ganglia and of motoneurons in spinal cord. Other neurotrophic factors such as CNTF, GDNF and LIF also exert a variety of actions on neuronal cells, which appear to overlap and complement those of the neurotrophins. In addition, there is an indirect contribution of GGF to nerve regeneration. GGF is produced by neurons and stimulates proliferation of Schwann cells, underlining the close interaction between neuronal and glial cells during peripheral nerve regeneration. Different possibilities have been investigated for the delivery of growth factors to the injured neurons, in search of a suitable system for clinical applications. The studies reviewed in this article show the therapeutic potential of neurotrophic factors for the treatment of peripheral nerve injury and for neuropathies.

Keywords: Nerve injury, peripheral neuropathy
Abstract
Full Text
Selected References
Collaboration tool especially designed for Life Science professionals.Drag-and-drop any entity to your messages.