title: Novel Atraumatic End-to-Side Repair Model Exhibits Robust Collateral Sprouting Independent of Donor Fiber Injury.
abstract: BACKGROUND
  A central issue underlying end-to-side neurorrhaphy technique is whether injury to the donor nerve fibers is necessary for successful reinnervation of the recipient nerve. To address this question, the authors developed a novel atraumatic end-to-side neurorrhaphy model that uses the preexisting anatomical structure of the median nerve as the Y-chamber to study the mechanism of collateral sprouting.
  
  
  METHODS
  In this rat forelimb model, the authors transected the musculocutaneous nerve and the lateral head of the median nerve, and coapted their distal stumps together. In this model, the authors use the medial head of the median nerve as the donor nerve, and the lateral head of the median nerve (distal stump) as a Y-shaped chamber, which provided structural connection to the recipient musculocutaneous nerve in end-to-side fashion.
  
  
  RESULTS
  Three months after surgery, converging histologic, electrophysiologic, and behavioral observations confirmed the successful reinnervation of the recipient nerve. Retrograde labeling indicated that sensory fibers exhibited greater collateral sprouting than observed for motor fibers. Interestingly, fluorescence of these collateral sprouting fibers was present only when the median nerve lateral head was attached to the musculocutaneous nerve of the biceps, indicating that factors derived from the denervated tissue likely induced the collateral sprouting in this model.
  
  
  CONCLUSIONS
  The authors' findings provide strong evidence that collateral sprouting can be robustly initiated independent of donor nerve fiber injury. The authors' model can accelerate the understanding of the mechanism underlying end-to-side neurorrhaphy and the optimization of its clinical use.
authors.affiliation: Shanghai and Chengdu, People's Republic of China From the Department of Hand Surgery, Huashan Hospital, Fudan University; Key Laboratory of Hand Reconstruction, Ministry of Health; Shanghai Key Laboratory of Peripheral Nerve and Microsurgery; and the Department of Orthopedics, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital.
authors.forename: Qiyuan
authors.initials: Q
authors.lastname: Bao
authors.forename: Chengwei
authors.initials: C
authors.lastname: Xiao
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.forename: Yudong
authors.initials: Y
authors.lastname: Gu
mesh_terms: D000714:Anastomosis, Surgical / Q000379:methods; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D008475:Median Nerve / Q000293:injuries / Q000601:surgery*; D009138:Musculocutaneous Nerve / Q000293:injuries / Q000601:surgery*; D009412:Nerve Fibers / Q000473:pathology; D009416:Nerve Regeneration / Q000502:physiology*; D019635:Neurosurgical Procedures / Q000379:methods*; D059348:Peripheral Nerve Injuries / Q000601:surgery*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019651:Plastic Surgery Procedures / Q000379:methods*; D014459:Ulnar Nerve / Q000293:injuries / Q000601:surgery*
references.citation: Viterbo F, Amr AH, Stipp EJ, Reis FJ. End-to-side neurorrhaphy: Past, present, and future. Plast Reconstr Surg. 2009;124(Suppl):e351–e358
references.citation: Zhang Z, Johnson EO, Vekris MD, et al. Long-term evaluation of rabbit peripheral nerve repair with end-to-side neurorrhaphy in rabbits. Microsurgery. 2006;26:262–267
references.citation: Haninec P, Kaiser R. The end-to-side neurorrhaphy in axillary nerve reconstruction in patients with brachial plexus palsy. Plast Reconstr Surg. 2012;129:882e–883e
references.citation: Zheng MX, Xu WD, Shen YD, Xu JG, Gu YD. Reconstruction of elbow flexion by end-to-side neurorrhaphy in phrenic nerve transfer. Plast Reconstr Surg. 2012;129:573e–575e
references.citation: Frey M, Giovanoli P, Michaelidou M. Functional upgrading of partially recovered facial palsy by cross-face nerve grafting with distal end-to-side neurorrhaphy. Plast Reconstr Surg. 2006;117:597–608
references.citation: Beris AE, Lykissas MG. Chapter 13: Experimental results in end-to-side neurorrhaphy. Int Rev Neurobiol. 2009;87:269–279
references.citation: 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
references.citation: Viterbo F, Trindade JC, 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
references.citation: Viterbo F, Trindade JC, 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
references.citation: Bontioti E, Dahlin LB, Kataoka K, Kanje M. End-to-side nerve repair induces nuclear translocation of activating transcription factor 3. Scand J Plast Reconstr Surg Hand Surg. 2006;40:321–328
references.citation: Yan JG, Matloub HS, Sanger JR, Zhang LL, Riley DA, Jaradeh SS. A modified end-to-side method for peripheral nerve repair: Large epineurial window helicoid technique versus small epineurial window standard end-to-side technique. J Hand Surg Am. 2002;27:484–492
references.citation: 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
references.citation: Watanabe H, Ochiya T, Ueda S, et al. Differentiation of a hepatic phenotype after heterotropic transplantation of heart, kidney, brain, and skin tissues into liver in F344 rats. Biochem Biophys Res Commun. 2007;354:841–845
references.citation: Bertelli JA, Mira JC. 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
references.citation: Sananpanich K, Galea MP, Morrison WA, Messina A. Quantitative characterization of regenerating axons after end-to-side and end-to-end coaptation in a rat brachial plexus model: A retrograde tracer study. J Neurotrauma. 2007;24:864–875
references.citation: Wang M, Xu W, Zheng M, Teng F, Xu J, Gu Y. Phrenic nerve end-to-side neurotization in treating brachial plexus avulsion: An experimental study in rats. Ann Plast Surg. 2011;66:370–376
references.citation: Duraku LS, Hossaini M, Schüttenhelm BN, et al. Re-innervation patterns by peptidergic Substance-P, non-peptidergic P2X3, and myelinated NF-200 nerve fibers in epidermis and dermis of rats with neuropathic pain. Exp Neurol. 2013;241:13–24
references.citation: Magnani P, Cherian PV, Gould GW, Greene DA, Sima AA, Brosius FC III. Glucose transporters in rat peripheral nerve: Paranodal expression of GLUT1 and GLUT3. Metabolism. 1996;45:1466–1473
references.citation: Hirose T, Tani T, Shimada T, Ishizawa K, Shimada S, Sano T. Immunohistochemical demonstration of EMA/Glut1-positive perineurial cells and CD34-positive fibroblastic cells in peripheral nerve sheath tumors. Mod Pathol. 2003;16:293–298
references.citation: Haninec P, Dubový P, Sámal F, Houstava L, Stejskal L. Reinnervation of the rat musculocutaneous nerve stump after its direct reconnection with the C5 spinal cord segment by the nerve graft following avulsion of the ventral spinal roots: A comparison of intrathecal administration of brain-derived neurotrophic factor and Cerebrolysin. Exp Brain Res. 2004;159:425–432
references.citation: Sámal F, Haninec P, Raska O, Dubovy P. Quantitative assessment of the ability of collateral sprouting of the motor and primary sensory neurons after the end-to-side neurorrhaphy of the rat musculocutaneous nerve with the ulnar nerve. Ann Anat. 2006;188:337–344
references.citation: Sanapanich K, Morrison WA, Messina A. Physiologic and morphologic aspects of nerve regeneration after end-to-end or end-to-side coaptation in a rat model of brachial plexus injury. J Hand Surg Am. 2002;27:133–142
references.citation: Yu Q, Chen C, Zhang X, et al. Quantitative assessment of the motor-sensory specificity of the motor and primary sensory neurons after the end-to-side neurorrhaphy. J Reconstr Microsurg. 2013;29:579–586
references.citation: Battal MN, Hata Y. A review on the history of end-to-side neurorrhaphy. Plast Reconstr Surg. 1997;99:2110–2111
references.citation: Cederna PS, Kalliainen LK, Urbanchek MG, Rovak JM, Kuzon WM Jr. “Donor” muscle structure and function after end-to-side neurorrhaphy. Plast Reconstr Surg. 2001;107:789–796
references.citation: Haninec P, Kaiser R, Dubový P. A comparison of collateral sprouting of sensory and motor axons after end-to-side neurorrhaphy with and without the perineurial window. Plast Reconstr Surg. 2012;130:609–614
references.citation: Cederna PS. Discussion: A comparison of collateral sprouting of sensory and motor axons after end-to-side neurorrhaphy with and without the perineurial window. Plast Reconstr Surg. 2012;130:615–617
references.citation: Yan YH, Yan JG, Matloub HS, et al. Helicoid end-to-side and oblique attachment technique in repair of the musculocutaneous nerve injury with the phrenic nerve as a donor: An experimental study in rats. Microsurgery. 2011;31:122–129
references.citation: 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
references.citation: Brenner MJ, Dvali L, Hunter DA, Myckatyn TM, Mackinnon SE. Motor neuron regeneration through end-to-side repairs is a function of donor nerve axotomy. Plast Reconstr Surg. 2007;120:215–223
references.citation: Tam SL, Archibald V, Tyreman N, Gordon T. Tetrodotoxin prevents motor unit enlargement after partial denervation in rat hindlimb muscles. J Physiol. 2002;543:655–663
references.citation: Rafuse VF, Gordon T, Orozco R. Proportional enlargement of motor units after partial denervation of cat triceps surae muscles. J Neurophysiol. 1992;68:1261–1276
references.citation: Zele T, Sketelj J, Bajrović FF. Efficacy of fluorescent tracers in retrograde labeling of cutaneous afferent neurons in the rat. J Neurosci Methods. 2010;191:208–214
references.citation: Zhang Z, Soucacos PN, Beris AE, Bo J, Ioachim E, Johnson EO. Long-term evaluation of rat peripheral nerve repair with end-to-side neurorrhaphy. J Reconstr Microsurg. 2000;16:303–311