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Neuromuscular reinnervation efficacy using a YFP model

Published:October 21, 2020DOI:https://doi.org/10.1016/j.bjps.2020.10.004

      Summary

      Introduction

      The gold standard reconstruction for facial reanimation is the functional muscle transfer. The reinnervation of a muscle is never complete, and clinical results are variable with 20% not achieving a satisfactory outcome. We hypothesise that this may be due to a mismatch between the characteristics of the donor nerve and transferred muscle.

      Method

      81 YFP-16 and 14 YFP-H mice were studied in three intervention groups over three time periods. Two parameters were investigated: the number and surface area of reinnervated neuromuscular junctions and regenerating axons. An assessment was made of motor unit proportions.

      Results

      All cases of nerve repair and nerve graft, the neuromuscular junctions (NMJ) were completely reinnervated by regenerating axons. The number and calibre of the regenerating axons were significantly different from controls for both intervention groups. The motor units were smaller in both intervention groups.

      Discussion

      Reinnervation occurs after nerve repair or graft; however, the arbour was reinnervated by large numbers of much smaller axons. These axons showed some evidence of remodelling in the repair group, but not in the graft group. Neither group achieved the parameters of the control group. There were persistent qualitative changes to the morphology of both axons and junctions. Imaging documented both synkinesis and alterations that resemble those seen in ageing.

      Conclusion

      Overall, the efficacy of reinnervation is very high with all NMJ reoccupied by regenerating axons. The way small axons are remodelled is different in the nerve repairs compared with the nerve grafts.

      Keywords

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      References

        • Harrison D.H.
        • Grobbelaar A.O.
        Pectoralis minor muscle transfer for unilateral facial palsy reanimation: an experience of 35 years and 637 cases.
        J Plast Reconstr Aesthet Surg. 2012; 65: 845-850
        • Sunderland S.
        The anatomy and physiology of nerve injury.
        Muscle Nerve. 1990; 13: 771-784
        • Zeineh L.L.
        • Wilhelmi B.J.
        • Zook E.G
        Managing acute nerve injuries in extremities.
        Oper Tech Plast Reconstr Surg. 2002; 9: 111-116
        • Ashur H.
        • Vilner Y.
        • Finsterbush A.
        • Rousso M.
        • Weinberg H.
        • Devor M
        Extent of fiber regeneration after peripheral nerve repair: silicone splint vs. suture, gap repair vs. graft.
        Exp Neurol. 1987; 97: 365-374
        • MacQuillan A.H.F.
        • Grobbelaar A.O.
        Functional muscle transfer and the variance of reinnervating axonal load: part I. The facial nerve.
        Plast Reconstr Surg. 2008; 121: 1570
        • MacQuillan A.H.F.
        • Grobbelaar A.O.
        Functional muscle transfer and the variance of reinnervating axonal load: part II. Peripheral nerves.
        Plast Reconstr Surg. 2008; 121: 1708
        • Urso-Baiarda F.
        • Grobbelaar A.O.
        A comparison of one-versus two-stage surgery in an experimental model of functional muscle transfer with interposed nerve grafting.
        J Plast Reconstr Aesthet Surg. 2009; 62: 1042-1047
        • Jacobs J.M.
        • Laing J.H.E.
        • Harrison D.H
        Regeneration through a long nerve graft used in the correction of facial palsy: a qualitative and quantitative study.
        Brain. 1996; 119: 271
        • Brown M.C.
        • Ironton R.
        Sprouting and regression of neuromuscular synapses in partially denervated mammalian muscles.
        J Physiol. 1978; 278: 325-348
        • Rafuse V.F.
        • Gordon T.
        • Orozco R
        Proportional enlargement of motor units after partial denervation of cat triceps surae muscles.
        J Neurophysiol. 1992; 68: 1261-1276
        • Kawabuchi M.
        • Zhou C.J.
        • Wang S.
        • Nakamura K.
        • Liu W.T.
        • Hirata K
        The spatiotemporal relationship among schwann cells, axons and postsynaptic acetylcholine receptor regions during muscle reinnervation in aged rats.
        Anat Rec. 2001; 264: 183-202
        • Akaaboune M.
        • Grady R.M.
        • Turney S.
        • Sanes J.R.
        • Lichtman J.W
        Neurotransmitter receptor dynamics studied in vivo by reversible photo-unbinding of fluorescent ligands.
        Neuron. 2002; 34: 865-876
        • Feng G.
        • Mellor R.H.
        • Bernstein M.
        • Keller-Peck C.
        • Nguyen Q.T.
        • Wallace M.
        • et al.
        Imaging neuronal subsets in transgenic mice expressing multiple spectral variants of GFP.
        Neuron. 2000; 28: 41-51
        • Livet J.
        • Weissman T.A.
        • Kang H.
        • Draft R.W.
        • Lu J.
        • Bennis R.A.
        • et al.
        Transgenic strategies for combinatorial expression of fluorescent proteins in the nervous system.
        Nature. 2007; 450: 56-62
        • Lu J.
        • Fiala J.C.
        • Lichtman J.W
        Semi-automated reconstruction of neural processes from large numbers of fluorescence images.
        PLoS ONE. 2009; 4: e5655
        • Lichtman J.W.
        • Livet J.
        • Sanes J.R
        A technicolour approach to the connectome.
        Nat Rev Neurosci. 2008; 9: 417-422
        • Colman H.
        • Nabekura J.
        • Lichtman J.W
        Alterations in synaptic strength preceding axon withdrawal.
        Science. 1997; 275: 356
        • Bishop D.L.
        • Misgeld T.
        • Walsh M.K.
        • Gan W.B.
        • Lichtman J.W
        Axon branch removal at developing synapses by axosome shedding.
        Neuron. 2004; 44: 651-661
        • Balice-Gordon R.J.
        • Lichtman J.W.
        Long-term synapse loss induced by focal blockade of postsynaptic receptors.
        Nature. 1994; 372: 519-524
        • Colman H.
        • Lichtman J.W.
        Cartellian competition at the neuromuscular junction.
        Trends Neurosci. 1992; 15: 197-199
        • Draft R.W.
        • Lichtman J.W.
        It's lonely at the top: winning climbing fibers ascend dendrites solo.
        Neuron. 2009; 63: 6-8
        • Lichtman J.W.
        • Colman H
        Synapse elimination and indelible memory.
        Neuron. 2000; 25: 269-278
      1. Rasband W.S., Image J. US National Institutes of Health, Bethesda, MD, USA 1997.

        • Balice-Gordon R.J.
        • Breedlove S.M.
        • Bernstein S.
        • Lichtman J.W
        Neuromuscular junctions shrink and expand as muscle fiber size is manipulated: in vivo observations in the androgen-sensitive bulbocavernosus muscle of mice.
        J Neurosci. 1990; 10: 2660-2671
        • Yushkevich P.A.
        • Piven J.
        • Hazlett H.C.
        • Smith R.G.
        • Ho S.
        • Gee J.C.
        • Gerig G
        User-guided 3D active contour segmentation of anatomical structures: significantly improved efficiency and reliability.
        Neuroimage. 2006; 31: 1116-1128
        • Balice-Gordon R.J.
        • Lichtman J.W.
        Long-term synapse loss induced by focal blockade of postsynaptic receptors.
        Nature. 1994; 372: 519-524
        • Keller-Peck C.R.
        • Walsh M.K.
        • Gan W.B.
        • Feng G.
        • Sanes J.R.
        • Lichtman J.W
        Asynchronous synapse elimination in neonatal motor units: studies using GFP transgenic mice.
        Neuron. 2001; 31: 381-394
        • Buffelli M.
        Activity-dependent synaptic competition at mammalian neuromuscular junctions.
        News Physiol Sci. 2004; 19: 85-91
        • Wood M.D.
        • Kemp S.W.
        • Weber C.
        • Borschel G.H.
        • Gordon T
        Outcome measures of peripheral nerve regeneration.
        Ann Anat. 2011; 193: 321-333
        • Kang H.
        • Tian L.
        • Thompson W
        Terminal schwann cells guide the reinnervation of muscle after nerve injury.
        J Neurocytol. 2003; 32: 975-985
        • Fu S.Y.
        • Gordon T.
        Contributing factors to poor functional recovery after delayed nerve repair: prolonged denervation.
        J Neurosci. 1995; 15: 3886-3895
        • Pestronk A.
        • Drachman D.B.
        • Griffin J.W
        Effects of aging on nerve sprouting and regeneration.
        Exp Neurol. 1980; 70: 65-82
        • Jacob J.M.
        • Robbins N.
        Age differences in morphology of reinnervation of partially denervated mouse muscle.
        J Neurosci. 1990; 10: 1530-1540
        • SHAWE G.D.
        On the number of branches formed by regenerating nerve-fibres.
        Br J Surg. 1955; 42: 474-488
        • Rich M.M.
        • Lichtman J.W.
        In vivo visualization of pre- and postsynaptic changes during synapse elimination in reinnervated mouse muscle.
        J Neurosci. 1989; 9: 1781-1805
        • Urbanchek M.G.
        • Kung T.A.
        • Frost C.M.
        • Martin D.C.
        • Larkin L.M.
        • Wollstein A.
        • Cederna P.S
        Development of a regenerative peripheral nerve interface for control of a neuroprosthetic limb.
        Biomed Res Int. 2016; 20165726730
        • Hargrove L.J.
        • Miller L.A.
        • Turner K.
        • Kuiken T.A
        Myoelectric pattern recognition outperforms direct control for transhumeral amputees with targeted muscle reinnervation: a randomized clinical trial.
        Sci Rep. 2017; 7: 13840
        • Fracol M.E.
        • Janes L.E.
        • Ko J.H.
        • Dumanian G.A
        "Targeted muscle reinnervation in the lower leg: an anatomic study".
        PRS. Oct 2018; 142: 541e-550e