Functional recovery of transected nerves treated with systemic BDNF and CNTF
Elbert T. Cheng M.D.
Division of Otolaryngology/Head and Neck Surgery, Stanford University Medical Center, Stanford, CA
Search for more papers by this authorDavid S. Utley M.D.
Division of Otolaryngology/Head and Neck Surgery, Stanford University Medical Center, Stanford, CA
Search for more papers by this authorPei-Ran Ho
Division of Otolaryngology/Head and Neck Surgery, Stanford University Medical Center, Stanford, CA
Search for more papers by this authorDerjung M. Tarn
Division of Otolaryngology/Head and Neck Surgery, Stanford University Medical Center, Stanford, CA
Search for more papers by this authorGrace M. Coan
Division of Otolaryngology/Head and Neck Surgery, Stanford University Medical Center, Stanford, CA
Search for more papers by this authorA. Neil Verity Ph.D.
Department of Neurobiology, Stanford University Medical Center, Stanford, CA
Search for more papers by this authorDavid H. Sierra
Division of Otolaryngology/Head and Neck Surgery, Stanford University Medical Center, Stanford, CA
Search for more papers by this authorCorresponding Author
David J. Terris M.D.
Division of Otolaryngology/Head and Neck Surgery, Stanford University Medical Center, Stanford, CA
Edwards Building, Stanford University Medical Center, Stanford, CA 94305-5328Search for more papers by this authorElbert T. Cheng M.D.
Division of Otolaryngology/Head and Neck Surgery, Stanford University Medical Center, Stanford, CA
Search for more papers by this authorDavid S. Utley M.D.
Division of Otolaryngology/Head and Neck Surgery, Stanford University Medical Center, Stanford, CA
Search for more papers by this authorPei-Ran Ho
Division of Otolaryngology/Head and Neck Surgery, Stanford University Medical Center, Stanford, CA
Search for more papers by this authorDerjung M. Tarn
Division of Otolaryngology/Head and Neck Surgery, Stanford University Medical Center, Stanford, CA
Search for more papers by this authorGrace M. Coan
Division of Otolaryngology/Head and Neck Surgery, Stanford University Medical Center, Stanford, CA
Search for more papers by this authorA. Neil Verity Ph.D.
Department of Neurobiology, Stanford University Medical Center, Stanford, CA
Search for more papers by this authorDavid H. Sierra
Division of Otolaryngology/Head and Neck Surgery, Stanford University Medical Center, Stanford, CA
Search for more papers by this authorCorresponding Author
David J. Terris M.D.
Division of Otolaryngology/Head and Neck Surgery, Stanford University Medical Center, Stanford, CA
Edwards Building, Stanford University Medical Center, Stanford, CA 94305-5328Search for more papers by this authorAbstract
The purpose of this study was to investigate the effect of systemic co-injections of ciliary neurotrophic factor (CNTF) and brain-derived neurotrophic factor (BDNF) on the functional recovery of transected sciatic nerves repaired by epineurial coaptation (EC) or collagen tubulization (CT). Forty Sprague-Dawley rats underwent transection of their sciatic nerves and repair by either EC or CT. With each repair technique, systemic injections of neurotrophic factors or control injections of lactated Ringer's solution were given. This resulted in four treatment groups: EC, EC + BDNF/CNTF, CT, and CT + BDNF/CNTF. Nerve function was assessed using sciatic functional indices (SFI). Animals whose nerves were repaired by CT (P = 0.01), CT + BDNF/CNTF (P = 0.04), and EC + BDNF/CNTF (P = 0.04) all had better functional recovery than those whose nerves were repaired by EC. There were no significant differences among these three groups, however. Animals in the CT group manifested the most rapid rate of recovery (P = 0.02 compared with EC). Collagen tubulization and systemic co-injections of BDNF/CNTF improve the rate and extent of sciatic functional recovery after nerve repair. The improvement in recovery conferred is not additive. © 1998 Wiley-Liss, Inc. MICROSURGERY 18:35–41, 1998.
References
- 1 Levi-Montalcini R: The nerve growth factor: Thirty-five years later. EMBO J 6: 1145–1154, 1987.
- 2 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 119: 45–54, 1992.
- 3 Holtzman DM, Mobley WC: Neurotrophic factors and neurological disease. West J Med 161: 246–254, 1994.
- 4 Barde Y-A, Edgar D, Thoenen H: Purification of a new neurotrophic factor from mammalian brain. EMBO J 1: 549–553, 1982.
- 5 Oppenheim EQ, Yin Q, Prevette D, Yan Q: Brain-derived neurotrophic factor rescues developing avian motoneurons from cell death. Nature 360: 755–757, 1992.
- 6 Stockli KA, Lillien LE, Naher-Noe M, et al: Regional distribution, developmental changes, and cellular localization of CNTF-mRNA and protein in the rat brain. J Cell Biol 115: 447–459, 1991.
- 7 Takahashi JB, Hoshimaru M, Kikuchi H, Hatanaka M: Extension of optic nerve fibers on genetically modified cells producing brain-derived neurotrophic factor. Neurosci Lett 149: 83–86, 1993.
- 8 Koliatsos VE, Clatterbuck RE, Winslow JW, Cayouette MH, Price DL: Evidence that brain-derived neurotrophic factor is a trophic factor for motor neurons in vivo. Neuron 40: 359–367, 1993.
- 9 Sendtner M, Holtmann B, Kolbeck R, Thoenen H, Barde Y-A: Brainderived neurotrophic factor prevents the death of motor neurons in newborn rats after nerve section. Nature 360: 757–759, 1992.
- 10 Yan Q, Elliot J, Snider WD: Brain-derived neurotrophic factor rescues spinal motor neuron from axotomy-induced cell death. Nature 360: 753–755, 1992.
- 11 Nishi R: Neurotophic factors: Two are better than one. Science 265: 1052–1053, 1994.
- 12
Utley DS,
Cheng ET,
Lewin SL,
Verity AN,
Sierra DH,
Terris DJ:
Brain-derived neurotrophic factor and collagen tubulization enhance functional recovery after peripheral nerve transection and repair.
Arch Otolaryngol Head Neck Surg
112:
407–413,
1996.
10.1001/archotol.1996.01890160047009 Google Scholar
- 13 Arakawa Y, Sendtner M, Thoenen H: Survival effect of ciliary neurotrophic factor on chick embryonic motoneurons in culture: Comparison with other neurotrophic factors and cytokines. J Neurosci 10: 3507–3515, 1990.
- 14 Helgren ME, Squinto SP, Davis HL, et al: Trophic effect of ciliary neurotrophic factor on denervated skeletal muscle. Cell 76: 493–504, 1994.
- 15 Sendtner M, Kreutzberg G, Thoenen H: Ciliary neurotrophic factor prevents the degeneration of motor neurons after axotomy. Nature 345: 440–441, 1990.
- 16 Oppenheim EQ, Prevette D, Haverkamp LJ, Houenou L, Yin Q-W, McManaman J: Biological studies of a putative avian muscle-derived neurotrophic factor that prevents naturally occurring motoneuron death in vivo. J Neurobiol 24: 1065–1079, 1993.
- 17 Newman JP, Verity AN, Hawatmeh S, Fee WE Jr, Terris DJ: Ciliary neurotrophic factor enhances peripheral nerve regeneration. Arch Otolaryngol Head Neck Surg 122: 399–403, 1996.
- 18 Mitsumoto H, Ikeda K, Klinkosz B, Cedarbaum JM, Wong V, Lindsay RM: Arrest of motor neuron disease in wobbler mice cotreated with CNTF and BDNF. Science 265: 1107–1110, 1994.
- 19 Lewin SL, Utley DS, Cheng ET, Verity AN, Terris DJ: Simultaneous treatment with BDNF and CNTF after peripheral nerve transection and repair enhances the rate of functional recovery compared with BDNF treatment alone. Laryngoscope 107: 992–999, 1997.
- 20 de Medinaceli L, Freed W, Wyatt R: An index of the functional condition of rat sciatic nerve based on measurements made from walking tracks. Neurol 77: 634–643, 1982.
- 21 Bain JR, MacKinnon SE, Hunter DA: Functional evaluation of complete sciatic, peroneal, and posterior tibial nerve lesions in the rat. Plast Reconstr Surg 83: 129–136, 1989.
- 22 Carlton JM, Goldberg NH: Quantitating integrated muscle function following reinnervation. Surg Forum 37: 611–612, 1986.
- 23 Clatterbuck RE, Price DL, Koliatsos VE: Ciliary neurotrophic factor prevents retrograde neuronal death in the adult central nervous system. Proc Natl Acad Sci USA 80: 2222–2226, 1993.
- 24 Ip NY, Yancopoulos GD: Ciliary neurotrophic factor and its receptor complex. Prog Growth Factor Res 4: 139–155, 1992.
- 25 Henderson E, Camu W, Mettling C, et al: Neurotrophins promote motor neuron survival and are present in embryonic limb bud. Nature 363: 266–270, 1993.
- 26 Cheng ET, Utley DS, Tarn DM, Ho PR, Verity AN, Terris DJ: Functional recovery following nerve injury and repair by silicon tubulization: Comparison of laminin-fibronectin, dialyzed plasma, collagen gel, and phosphate buffered saline. (Submitted).
- 27 Muller HW, Ignatius MJ, Hangen DH, Shooter EM: Expression of specific sheath cell proteins during nerve growth and regeneration in mammals. J Cell Biol 102: 393–403, 1986.
- 28 Snipes GJ, Suter U: Signaling pathways mediating axon-Schwann cell interactions. Trends Neurosci 17: 399–401, 1994.
- 29 Henderson JT, Seniuk NA, Richardson PM, Gauldie J, Roder JC: Systemic administration of ciliary neurotrophic factor induces cachexia in rodents. J Clin Invest 93: 2632–2638, 1994.
Citing Literature
