J Reconstr Microsurg 2009; 25(5): 295-306
DOI: 10.1055/s-0029-1202554
© Thieme Medical Publishers

Effect of Donor Nerve Injury Distal to an End-to-Side Neurorrhaphy Model

Zinon T. Kokkalis1 , Panayiotis N. Soucacos2 , Julia K. Terzis1
  • 1International Institute of Reconstructive Microsurgery, Eastern Virginia Medical School, Norfolk, Virginia
  • 2Department of Orthopaedic Surgery, University of Athens, School of Medicine, Athens, Greece
Further Information

Publication History

Publication Date:
13 March 2009 (online)

ABSTRACT

In end-to-side neurorrhaphy, “noninjury” models of the donor nerve do not seem to offer worthwhile functional outcomes. The role of donor nerve injury distal to the coaptation site remains unclear. End-to-side neurorrhaphy was studied in a rat model in which the proximal stump of the transected musculocutaneous nerve was sutured to the median nerve by end-to-side coaptation. Twenty Sprague-Dawley rats were randomized to four groups of five animals each, in which three different types of donor injury (crush, ligation, or transection injury) distal to the coaptation site were executed; findings were compared with a similar end-to-side model without donor nerve injury (control). Behavioral analysis, electrophysiological studies, muscle morphometric studies, and nerve fibers counts showed no significant differences among groups. However, there was a significant difference regarding mean myelin area (p = 0.0362) and mean fiber diameter (p = 0.0159) for the crush injury group as compared with the control group. No significant differences were found among the other groups. These data suggest that donor crush injury distal to the coaptation site may increase the rate of myelin formation in regenerating axons across an end-to-side model; however, at 4 weeks of follow-up, there was no significant behavioral or functional significance in this treatment group.

REFERENCES

  • 1 Letievant E. Traite des Sections Nerveuses. Paris; J.B. Bailliere et Fils 1873
  • 2 Papalia I, Geuna S, D'Alcontres F S, Tos P. Origin and history of end-to-side neurorrhaphy.  Microsurgery. 2007;  27 56-61
  • 3 Zhang F, Fischer K A. End-to-side neurorrhaphy.  Microsurgery. 2002;  22 122-127
  • 4 Viterbo F, Trindade J C, Hoshino K, Mazzoni Neto A. Latero-terminal neurorrhaphy without removal of the epineural sheath. Experimental study in rats.  Rev Paul Med. 1992;  110 267-275
  • 5 Viterbo F, Trindade J C, Hoshino K, Mazzoni Neto A. End-to-side neurorrhaphy with removal of the epineurial sheath: an experimental study in rats.  Plast Reconstr Surg. 1994;  94 1038-1047
  • 6 Lundborg G, Zhao Q, Kanje M, Danielsen N, Kerns J M. Can sensory and motor collateral sprouting be induced from intact peripheral nerve by end-to-side anastomosis?.  J Hand Surg [Br]. 1994;  19 277-282
  • 7 Noah E M, Williams A, Jorgenson C, Skoulis T G, Terzis J K. End-to-side neurorrhaphy: a histologic and morphometric study of axonal sprouting into an end-to-side nerve graft.  J Reconstr Microsurg. 1997;  13 99-106
  • 8 Caplan J, Tiangco D A, Terzis J K. Effects of IGF-II in a new end-to-side model.  J Reconstr Microsurg. 1999;  15 351-358
  • 9 Hayashi A, Yanai A, Komuro Y, Nishida M, Inoue M, Seki T. Collateral sprouting occurs following end-to-side neurorrhaphy.  Plast Reconstr Surg. 2004;  114 129-137
  • 10 Tiangco D A, Papakonstantinou K C, Mullinax K A, Terzis J K. IGF-I and end-to-side nerve repair: a dose-response study.  J Reconstr Microsurg. 2001;  17 247-256
  • 11 Bontioti E, Kanje M, Lundborg G, Dahlin L B. End-to-side nerve repair in the upper extremity of rat.  J Peripher Nerv Syst. 2005;  10 58-68
  • 12 Adelson P D, Bonaroti E A, Thompson T P, Tran M, Nystrom N A. End-to-side neurorrhaphies in a rodent model of peripheral nerve injury: a preliminary report of a novel technique.  J Neurosurg. 2004;  101(1 Suppl) 78-84
  • 13 Giovanoli P, Koller R, Meuli-Simmen C et al.. Functional and morphometric evaluation of end-to-side neurorrhaphy for muscle reinnervation.  Plast Reconstr Surg. 2000;  106 383-392
  • 14 Amr S M, Moharram A N. Repair of brachial plexus lesions by end-to-side side-to-side grafting neurorrhaphy: experience based on 11 cases.  Microsurgery. 2005;  25 126-146
  • 15 Yuksel F, Peker F, Celikoz B. Two applications of end-to-side nerve neurorrhaphy in severe upper-extremity nerve injuries.  Microsurgery. 2004;  24 363-368
  • 16 Haninec P, Samal F, Tomas R, Houstava L, Dubovwy P. Direct repair (nerve grafting), neurotization, and end-to-side neurorrhaphy in the treatment of brachial plexus injury.  J Neurosurg. 2007;  106 391-399
  • 17 Bertelli J A, Ghizoni M F. Concepts of nerve regeneration and repair applied to brachial plexus reconstruction.  Microsurgery. 2006;  26 230-244
  • 18 Bertelli J A, Ghizoni M F. Nerve repair by end-to-side coaptation or fascicular transfer: a clinical study.  J Reconstr Microsurg. 2003;  19 313-318
  • 19 Isaacs J, Allen D, Chen L E, Nunley II J. Reverse end-to-side neurotization.  J Reconstr Microsurg. 2005;  21 43-48
  • 20 Fujiwara T, Matsuda K, Kubo T et al.. Axonal supercharging technique using reverse end-to-side neurorrhaphy in peripheral nerve repair: an experimental study in the rat model.  J Neurosurg. 2007;  107 821-829
  • 21 Kerns J M, Sladek E H, Malushte T S et al.. End-to-side nerve grafting of the tibial nerve to bridge a neuroma-in-continuity.  Microsurgery. 2005;  25 155-164
  • 22 Grossman J A, DiTaranto P, Yaylali I, Alfonso I, Ramos L E, Price A E. Shoulder function following late neurolysis and bypass grafting for upper brachial plexus birth injuries.  J Hand Surg [Br]. 2004;  29 356-358
  • 23 Amr S M, Moharram A N, Abdel-Meguid K M. Augmentation of partially regenerated nerves by end-to-side side-to-side grafting neurotization: experience based on eight late obstetric brachial plexus cases.  J Brachial Plex Peripher Nerve Inj. 2006;  1 6
  • 24 Sugimoto Y, Takayama S, Horiuchi Y, Toyama Y. An experimental study on the perineurial window.  J Peripher Nerv Syst. 2002;  7 104-111
  • 25 Walker J C, Brenner M J, Mackinnon S E, Winograd J M, Hunter D A. Effect of perineurial window size on nerve regeneration, blood-nerve barrier integrity, and functional recovery.  J Neurotrauma. 2004;  21 217-227
  • 26 Noah E M, Williams A, Fortes W, Terzis J K. A new animal model to investigate axonal sprouting after end-to-side neurorrhaphy.  J Reconstr Microsurg. 1997;  13 317-325
  • 27 Okajima S, Terzis J K. Ultrastructure of early axonal regeneration in an end-to-side neurorrhaphy model.  J Reconstr Microsurg. 2000;  16 313-323
  • 28 McCallister W V, Tang P, Trumble T E. Is end-to-side neurorrhaphy effective? A study of axonal sprouting stimulated from intact nerves.  J Reconstr Microsurg. 1999;  15 597-603
  • 29 Brenner M J, Dvali L, Hunter D A, Myckatyn T M, Mackinnon S E. Motor neuron regeneration through end-to-side repairs is a function of donor nerve axotomy.  Plast Reconstr Surg. 2007;  120 215-223
  • 30 Bertelli J A, Taleb M, Saadi A, Mira J C, Pecot-Dechavassine M. The rat brachial plexus and its terminal branches: an experimental model for the study of peripheral nerve regeneration.  Microsurgery. 1995;  16 77-85
  • 31 Inciong J G, Marrocco W C, Terzis J K. Efficacy of intervention strategies in a brachial plexus global avulsion model in the rat.  Plast Reconstr Surg. 2000;  105 2059-2071
  • 32 Bennett G J, Xie Y K. A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man.  Pain. 1988;  33 87-107
  • 33 Bertelli J A, Mira J C. Behavioral evaluating methods in the objective clinical assessment of motor function after experimental brachial plexus reconstruction in the rat.  J Neurosci Methods. 1993;  46 203-208
  • 34 Gorio A, Carmignoto G, Finesso M, Polato P, Nunzi M G. Muscle reinnervation–II. Sprouting, synapse formation and repression.  Neuroscience. 1983;  8 403-416
  • 35 Slack J R, Hopkins W G, Williams M N. Nerve sheaths and motoneurone collateral sprouting.  Nature. 1979;  282 506-507
  • 36 Buehler M J, Seaber A V, Urbaniak J R. The relationship of functional return to varying methods of nerve repair.  J Reconstr Microsurg. 1990;  6 61-69
  • 37 Fortes W M, Noah E M, Liuzzi F J, Terzis J K. End-to-side neurorrhaphy: evaluation of axonal response and upregulation of IGF-I and IGF-II in a non-injury model.  J Reconstr Microsurg. 1999;  15 449-457
  • 38 Gurney M E, Yamamoto H, Kwon Y. Induction of motor neuron sprouting in vivo by ciliary neurotrophic factor and basic fibroblast growth factor.  J Neurosci. 1992;  12 3241-3247
  • 39 Akeda K, Hirata H, Matsumoto M et al.. Regenerating axons emerge far proximal to the coaptation site in end-to-side nerve coaptation without a perineurial window using a T-shaped chamber.  Plast Reconstr Surg. 2006;  117 1194-1203
  • 40 al-Qattan M M, al-Thunyan A. Variables affecting axonal regeneration following end-to-side neurorrhaphy.  Br J Plast Surg. 1998;  51 238-242
  • 41 Spencer P S, Weinberg H J, Raine C S, Prineas J W. The perineurial window—a new model of focal demyelination and remyelination.  Brain Res. 1975;  96 323-329
  • 42 Tarasidis G, Watanabe O, Mackinnon S E, Strasberg S R, Haughey B H, Hunter D A. End-to-side neurorraphy: a long-term study of neural regeneration in a rat model.  Otolaryngol Head Neck Surg. 1998;  119 337-341
  • 43 Tarasidis G, Watanabe O, Mackinnon S E, Strasberg S R, Haughey B H, Hunter D A. End-to-side neurorrhaphy resulting in limited sensory axonal regeneration in a rat model.  Ann Otol Rhinol Laryngol. 1997;  106 506-512
  • 44 Hayashi A, Pannucci C, Moradzadeh A et al.. Axotomy or compression is required for axonal sprouting following end-to-side neurorrhaphy.  Exp Neurol. 2008;  211 539-550
  • 45 Durrenberger P F, Facer P, Gray R A et al.. Cyclooxygenase-2 (Cox-2) in injured human nerve and a rat model of nerve injury.  J Peripher Nerv Syst. 2004;  9 15-25
  • 46 Durrenberger P F, Facer P, Casula M A et al.. Prostanoid receptor EP1 and Cox-2 in injured human nerves and a rat model of nerve injury: a time-course study.  BMC Neurol. 2006;  9 15-25
  • 47 Komori N, Takemori N, Kim H K et al.. Proteomics study of neuropathic and nonneuropathic dorsal root ganglia: altered protein regulation following segmental spinal nerve ligation injury.  Physiol Genomics. 2007;  29 215-230
  • 48 Lee D H, Iyengar S, Lodge D. The role of uninjured nerve in spinal nerve ligated rats points to an improved animal model of neuropathic pain.  Eur J Pain. 2003;  7 473-479
  • 49 DeLeo J A, Yezierski R P. The role of neuroinflammation and neuroimmune activation in persistent pain.  Pain. 2001;  90 1-6
  • 50 Shu X Q, Mendell L M. Neurotrophins and hyperalgesia.  Proc Natl Acad Sci U S A. 1999;  96 7693-7696
  • 51 Kontinen V K, Paananen S, Kalso E. The effects of the alpha2-adrenergic agonist, dexmedetomidine, in the spinal nerve ligation model of neuropathic pain in rats.  Anesth Analg. 1998;  86 355-360
  • 52 Hoffman P N, Griffin J W, Price D L. Control of axonal caliber by neurofilament transport.  J Cell Biol. 1984;  99 705-714
  • 53 Hoffman P N, Cleveland D W, Griffin J W, Landes P W, Cowan N J, Price D L. Neurofilament gene expression: a major determinant of axonal caliber.  Proc Natl Acad Sci U S A. 1987;  84 3472-3476
  • 54 Havton L A, Hotson J R, Kellerth J O. Partial peripheral motor nerve lesions induce changes in the conduction properties of remaining intact motoneurons.  Muscle Nerve. 2001;  24 662-666
  • 55 Mackinnon S E, Dellon A L. Surgery of the Peripheral Nerve. New York; Thieme 1988
  • 56 Magill C K, Tong A, Kawamura D et al.. Reinnervation of the tibialis anterior following sciatic nerve crush injury: a confocal microscopic study in transgenic mice.  Exp Neurol. 2007;  207 64-74
  • 57 Hopkins W G, Slack J R. The sequential development of nodal sprouts in mouse muscles in response to nerve degeneration.  J Neurocytol. 1981;  10 537-556
  • 58 Nauta H J, Pritz M B, Lasek R J. Afferents to the rat caudoputamen studied with horseradish peroxidase: an evaluation of retrograde neuroanatomical research methods.  Brain Res. 1974;  67 219-238
  • 59 Johnson E O, Zoubos A B, Soucacos P N. Regeneration and repair of peripheral nerves.  Injury. 2005;  36(Suppl 4) S24-S29
  • 60 Pannucci C, Myckatyn T M, Mackinnon S E, Hayashi A. End-to-side nerve repair: review of the literature.  Restor Neurol Neurosci. 2007;  25 45-63
  • 61 Fugleholm K, Schmalbruch H, Krarup C. Early peripheral nerve regeneration after crushing, sectioning, and freeze studied by implanted electrodes in the cat.  J Neurosci. 1994;  14 2659-2673
  • 62 McQuarrie I G. Effect of conditioning lesion on axonal sprout formation at nodes of Ranvier.  J Comp Neurol. 1985;  231 239-249
  • 63 Bontioti E N, Kanje M, Dahlin L B. Regeneration and functional recovery in the upper extremity of rats after various types of nerve injuries.  J Peripher Nerv Syst. 2003;  8 159-168
  • 64 Gu Y D, Ma M K. Nerve transfer for treatment of root avulsion of the brachial plexus: experimental studies in a rat model.  J Reconstr Microsurg. 1991;  7 15-22

Julia K TerzisM.D. Ph.D. 

Professor, Department of Surgery, Division of Plastic and Reconstructive Surgery, Eastern Virginia Medical School

700 Olney Road, LH 2055, Norfolk, Virginia 23501

Email: mrc@jkterzis.com

    >