Effect of surgically guided axonal regrowth into a 3-way-conduit (isogeneic trifurcated aorta) on functional recovery after facial-nerve reconstruction: Experimental study in rats
Restricted accessResearch articleFirst published online April 16, 2019
Effect of surgically guided axonal regrowth into a 3-way-conduit (isogeneic trifurcated aorta) on functional recovery after facial-nerve reconstruction: Experimental study in rats
The “post-paralytic syndrome” after facial nerve reconstruction has been attributed to (i) malfunctioning axonal guidance at the fascicular (branches) level, (ii) collateral branching of the transected axons at the lesion site, and (iii) intensive intramuscular terminal sprouting of regenerating axons which causes poly-innervation of the neuromuscular junctions (NMJ).
Objective:
The first two reasons were approached by an innovative technique which should provide the re-growing axons optimal conditions to elongate and selectively re-innervate their original muscle groups.
Methods:
The transected facial nerve trunk was inserted into a 3-way-conduit (from isogeneic rat abdominal aorta) which should “guide” the re-growing facial axons to the three main branches of the facial nerve (zygomatic, buccal and marginal mandibular). The effect of this method was tested also on hypoglossal axons after hypoglossal-facial anastomosis (HFA). Coaptational (classic) FFA (facial-facial anastomosis) and HFA served as controls.
Results:
When compared to their coaptation (classic) alternatives, both types of 3-way-conduit operations (FFA and HFA) promoted a trend for reduction in the collateral axonal branching (the proportion of double- or triple-labelled perikarya after retrograde tracing was slightly reduced). In contrast, poly-innervation of NMJ in the levator labii superioris muscle was increased and vibrissal (whisking) function was worsened.
Conclusions:
The use of 3-way-conduit provides no advantages to classic coaptation. Should the latter be impossible (too large interstump defects requiring too long interpositional nerve grafts), this type of reconstruction may be applied. (230 words)
AldskogiusH., ThomanderL. (1986). Selective reinnervation of somatotopically appropriate muscles after facial nerve transection and regeneration in the neonatal rat. Brain Research, 375(1), 126–134.
2.
AngelovD.N., CeynowaM., Guntinas-LichiusO., StreppelM., GroshevaM., KiryakovaS.I., SkourasE., MaegeleM., IrintchevA., NeissW.F., SinisN., AlvanouA., DunlopS.A. (2007). Mechanical stimulation of paralyzed vibrissal muscles following facial nerve injury in adult rat promotes full recovery of whisking. Neurobiology of Disease, 26(1), 229–242.
3.
AngelovD.N., Guntinas-LichiusO., WewetzerK., NeissW.F., StreppelM. (2005). Axonal branching and recovery of coordinated muscle activity after transection of the facial nerve in adult rats. In:
BeckF.F., ChristB., ClascáF., HainesD.E., KorfH.W., KummerW., MaraniE., PutzR., SanoY., SchieblerT.H., &
ZillersK., editors. Advances in Anatomy Embryology and Cell Biology. Berlin, Heidelberg, Germany: Springer Verlag, pp. 3–25
4.
BarryJ.A., RibchesterR.R. (1995). Persistent polyneuronal innervation in partially denervated rat muscle after reinnervation and recovery from prolonged nerve conduction block. The Journal of Neuroscience, 15(10), 6327–6339.
5.
BendellaH., BrackmannD.E., GoldbrunnerR., AngelovD.N. (2016). Nerve crush but not displacement-induced stretch of the intra-arachnoidal facial nerve promotes facial palsy after cerebellopontine angle surgery. Experimental Brain Research, 234(10), 2905–2913.
6.
BendellaH., RinkS., GroshevaM., SarikciogluL., GordonT., AngelovD.N. (2017). Putative roles of soluble trophic factors in facial nerve regeneration, target reinnervation, and recovery of vibrissal whisking. Experimental Neurology, 300, 100–110.
7.
BermejoR., HarveyM., GaoP., ZeiglerH.P. (1996). Conditioned whisking in the rat. Somatosensory and Motor Research, 13(3-4), 225–233.
8.
BischoffA., GroshevaM., IrintchevA., SkourasE., KaidoglouK., MichaelJ., AngelovaS.K., KuertenS., SinisN., DunlopS.A., AngelovD.N. (2009). Manual stimulation of the orbicularis oculi muscle improves eyelid closure after facial nerve injury in adult rats. Muscle & Nerve, 39(2), 197–205.
9.
BrownM.C., HollandR.L., HopkinsW.G., KeynesR.J. (1981). An assessment of the spread of the signal for terminal sprouting within and between muscles. Brain Research, 210(1-2), 145–151.
10.
BrushartT.M. (1987). Neurotropism and neurotrophism. The Journal of Hand Surgery, 12(5 Pt 1), 808–809.
11.
BrushartT.M. (1988). Preferential reinnervation of motor nerves by regenerating motor axons. The Journal of Neuroscience, 8(3), 1026–1031.
12.
BrushartT.M., GerberJ., KessensP., ChenY.G., RoyallR.M. (1998). Contributions of pathway and neuron to preferential motor reinnervation. The Journal of Neuroscience, 18(21), 8674–8681.
13.
BüngnerO. (1891). Ueber die Degenerations- und Regenerationsvorgänge am Nerven nach Verletzungen.. Beitråge Pathologische Anatomie, 10, 321–387.
14.
CarvellG.E., SimonsD.J. (1990). Biometric analyses of vibrissal tactile discrimination in the rat. The Journal of Neuroscience, 10(8), 2638–2648.
15.
CurleyJ.L., CatigG.C., Horn-RanneyE.L., MooreM.J. (2014). Sensory axon guidance with semaphorin 6A and nerve growth factor in a biomimetic choice point model. Biofabrication, 6(3), 035026.
16.
DohmS., StreppelM., Guntinas-LichiusO., PeshevaP., ProbstmeierR., WaltherM., NeissW.F., StennertE., AngelovD.N. (2000). Local application of extracellular matrix proteins fails to reduce the number of axonal branches after varying reconstructive surgery on rat facial nerve. Restorative Neurology and Neuroscience, 16(2), 117–126.
17.
DorflJ. (1985). The innervation of the mystacial region of the white mouse: A topographical study. Journal of Anatomy, 142, 173–184.
18.
EsslenE. (1960). Electromyographic findings on two types of misdirection of regenerating axons. Electroencephalography and Clinical Neurophysiology, 12, 738–741.
19.
EvgenievaE., SchweigertP., Guntinas-LichiusO., PavlovS., GroshevaM., AngelovaS., StreppelM., IrintchevA., SkourasE., KuertenS., SinisN., DunlopS., RadevaV., AngelovD.N. (2008). Manual stimulation of the suprahyoid-sublingual region diminishes polynnervation of the motor endplates and improves recovery of function after hypoglossal nerve injury in rats. Neurorehabilitation and Neural Repair, 22(6), 754–768.
20.
FansaH., KeilhoffG., PlogmeierK., FrerichsO., WolfG., SchneiderW. (1999). Successful implantation of Schwann cells in acellular muscles. Journal of Reconstructive Microsurgery, 15(1), 61–65.
21.
FansaH., KeilhoffG., WolfG., SchneiderW., GoldB.G. (2001). Tissue Engineering of Peripheral Nerves: A Comparison of Venous and Acellular Muscle Grafts with Cultured Schwann Cells. Plastic and Reconstructive Surgery, 107(2), 495–496.
22.
FansaH., SchneiderW., WolfG., KeilhoffG. (2002). Influence of insulin-like growth factor-I (IGF-I) on nerve autografts and tissue-engineered nerve grafts. Muscle & Nerve, 26(1), 87–93.
23.
FriedeR.L., BischhausenR. (1980). The fine structure of stumps of transected nerve fibers in subserial sections. Journal of the Neurological Sciences, 44(2-3), 181–203.
GrantG.A., RostomilyR.R., KimD.K., MaybergM.R., FarrellD., AvellinoA., DuckertL.G., GatesG.A., WinnH.R. (2002). Delayed facial palsy after resection of vestibular schwannoma. Journal of Neurosurgery, 97(1), 93–96.
26.
GreulichM. (2005). Anchoring the nasolabial fold. In:
BeurskensC.H.G., van Gelder R.S., HeymansG., ManniJ.J., NicolaiJ.P.A., editors. The Facial Palsies. Utrecht: Lemma Publishers. pp. 235–243.
27.
GrimbyG., EinarssonG., HedbergM., AnianssonA. (1989). Muscle adaptive changes in post-polio subjects. Scandinavian Journal of Rehabilitation Medicine, 21(1), 19–26.
28.
GroshevaM., RinkS., JansenR., BendellaH., PavlovS.P., SarikciogluL., AngelovD.N., DunlopS.A. (2018). Early and continued manual stimulation is required for long-term recovery after facial nerve injury. Muscle & Nerve, 57(1), 100–106.
29.
GuerrissiJ.O., Gil MirandaM.F. (2007). Intraneural topography of the extratemporal facial nerve: Microsurgical nerve reconstruction. Journal of Craniofacial Surgery, 18(3), 578–585.
30.
GundersenH.J. (1986). Stereology of arbitrary particles. A review of unbiased number and size estimators and the presentation of some new ones, in memory of William R. Thompson. Journal of Microscopy, 143(Pt 1), 3–45.
31.
Guntinas-LichiusO., AngelovD.N., TomovT.L., DramigaJ., NeissW.F., WewetzerK. (2001). Transplantation of olfactory ensheathing cells stimulates the collateral sprouting from axotomized adult rat facial motoneurons. Experimental Neurology, 172(1), 70–80.
32.
Guntinas-LichiusO., HundeshagenG., PalingT., StreppelM., GroshevaM., IrintchevA., SkourasE., AlvanouA., AngelovaS., KuertenS., SinisN., DunlopS.S., AngelovD.N. (2007). Manual stimulation of facial muscles improves functional recovery after hypoglossal-facial anastomosis and interpositional nerve grafting of the facial nerve in adult rats. Neurobiology of Disease, 28(1), 101–112.
33.
Guntinas-LichiusO., IrintchevA., StreppelM., LenzenM., GroshevaM., WewetzerK., NeissW.F., AngelovD.N. (2005). Factors limiting motor recovery after facial nerve transection in the rat: Combined structural and functional analyses. European Journal of Neuroscience, 21(2), 391–402.
34.
Guntinas-LichiusO., WewetzerK., TomovT.L., AzzolinN., KazemiS., StreppelM., NeissW.F., AngelovD.N. (2002). Transplantation of olfactory mucosa minimizes axonal branching and promotes the recovery of vibrissae motor performance after facial nerve repair in rats. The Journal of Neuroscience, 22(16), 7121–7131.
35.
HadlockT., ElisseeffJ., LangerR., VacantiJ., CheneyM. (1998). A tissue-engineered conduit for peripheral nerve repair. Archives of Otolaryngology Head & Neck Surgery, 124(10), 1081–1086.
36.
HizayA., OzsoyU., DemirelB.M., OzsoyO., AngelovaS.K., AnkerneJ., SarikciogluS.B., DunlopS.A., AngelovD.N., SarikciogluL. (2012). Use of a Y-tube conduit after facial nerve injury reduces collateral axonal branching at the lesion site but neither reduces polyinnervation of motor endplates nor improves functional recovery. Neurosurgery, 70(6), 1544–1556.
37.
HristovT., Guntinas-LichiusO., SmithG., AngelovD.N. (2005). Focal application of the cell signaling molecules semaphorin-3A and neuropilin-1 fails to improve recovery of function after peripheral nerve lesion. 22. Arbeitstagung der Anatomischen Gesellschaft, Würzburg. 28. bis 30. September 2005. 62 [Abstract].
HudsonT.W., EvansG.R., &
SchmidtC.E. (2000). Engineering strategies for peripheral nerve repair. Orthopedic Clinics of North America, 31(3), 485–498.
40.
HwangK., KimS.G., KimD.J. (2006). Facial-hypoglossal nerve anastomosis using laser nerv welding. Journal of Craniofacial Surgery, 17(4), 687–691.
41.
Ijkema-PaassenJ., MeekM.F., GramsbergenA. (2002). Reinnervation of muscles after transection of the sciatic nerve in adult rats. Muscle & Nerve, 25(6), 891–897.
42.
ItoM., KudoM. (1994). Reinnervation by axon collaterals from single facial motoneurons to multiple muscle targets following axotomy in the adult guinea pig. Acta Anatomica (Basel), 151(2), 124–130.
43.
Jergovic< <, D., StalP., LidmanD., LindvallB., HildebrandC. (2001). Changes in a rat facial muscle after facial nerve injury and repair. Muscle & Nerve, 24(9), 1202–1212.
44.
JohnsonE.O., SoucacosP.N. (2008). Nerve repair: Experimental and clinical evaluation of biodegradable artificial nerve guides. (Suppl)S30–36.
45.
KerrebijnJ.D., FreemanJ.L. (1998). Facial nerve reconstruction: Outcome and failures. The Journal of Otolaryngology, 27(4), 183–186.
46.
KitaharaA.K., SuzukiY., QiP., NishimuraY., SuzukiK., KiyotaniT., TakimotoY., NakamuraT., ShimizuY., EndoK. (1999). Facial nerve repair using a collagen conduit in cats. Scandinavian Journal of Plastic and Reconstructive Surgery and Hand Surgery, 33(2), 187–193.
47.
KleinB.G., RhoadesR.W. (1985). Representation of whisker follicle intrinsic musculature in the facial motor nucleus of the rat. The Journal of Comparative Neurology, 232(1), 55–69.
48.
KomisarukB.R. (1970). Synchrony between limbic system theta activity and rhythmical behavior in rats. Journal of Comparative and Physiological Psychology, 70(3), 482–492.
49.
LiuD., MiD., ZhangT., ZhangY., YanJ., WangY., TanX., YuanY., YangY., GuX., HuW. (2018). Tubulation repair mitigates misdirection of regenerating motor axons across a sciatic nerve gap in rats. Scientific Reports, 8(1), 3443.
50.
LundborgG., DahlinL.B., DanielsenN., NachemsonA.K. (1986). Tissue specificity in nerve regeneration. Scandinavian Journal of Plastic and Reconstructive Surgery, 20(3), 279–283.
51.
LundborgG., DahlinL., DanielsenN., ZhaoQ. (1994). Trophism, tropism, and specificity in nerve regeneration. Journal of Reconstructive Microsurgery, 10(5), 345–354.
52.
LundborgG., RosénB., DahlinL., DanielsenN., HolmbergJ. (1997). Tubular versus conventional repair of median and ulnar nerves in the human forearm: Early results from a prospective, randomized, clinical study. The Journal of Hand Surgery, 22(1), 99–106.
53.
MackinnonS.E., DellonA.L., LundborgG., HudsonA.R., HunterD.A. (1986). A study of neurotrophism in a primate model. The Journal of Hand Surgery, 11(6), 888–894.
54.
MackinnonS.E., DellonA.L., O’BrienJ.P. (1991). Changes in nerve fiber numbers distal to a nerve repair in the rat sciatic nerve model. Muscle & Nerve, 14(11), 1116–1122.
55.
MagillC.K., MooreA.M., BorschelG.H., MackinnonS.E. (2010). A new model for facial nerve research: The novel transgenic Thy1-GFP rat. Archives of Facial Plastic Surgery, 12(5), 315–320.
56.
OzsoyU., HizayA., DemirelB.M., OzsoyO., Bilmen SarikciogluS., TurhanM., SarikciogluL. (2011). The hypoglossal-facial nerve repair as a method to improve recovery of motor function after facial nerve injury. Annals of Anatomy, 193(4), 304–313.
57.
PolitisM.J. (1985). Specificity in mammalian peripheral nerve regeneration at the level of the nerve trunk. Brain Research, 328(2), 271–276.
58.
PolitisM.J., EderleK., SpencerP.S. (1982). Tropism in nerve regeneration in vivo. Attraction of regenerating axons by diffusible factors derived from cells in distal nerve stumps of transected peripheral nerves. Brain Research, 253(1-2), 1–12.
59.
RichM.M., LichtmanJ.W. (1989). In vivo visualization of pre- and postsynaptic changes during synapse elimination in reinnervated mouse muscle. The Journal of Neuroscience, 9(5), 1781–1805.
60.
RosenbergA.F., Isaacman-BeckJ., Franzini-ArmstrongC., GranatoM. (2014). Schwann cells and deleted in colorectal carcinoma direct regenerating motor axons towards their original path. The Journal of Neuroscience, 34(44), 14668–14681.
61.
SchröderJ.M. (1968a).
Die Hyperneurotisation Büngnerscher Bänder bei der experimentellen Isoniazid-Neuropathie: Phasenkontrast- und elektronenmikroskopische Untersuchungen. Virchows Archiv Abteilung, 1(1), 131–156.
62.
SeckelB.R., RyanS.E., GagneR.G., ChiuT.H., WatkinsE.Jr. (1986). Target-specific nerve regeneration through a nerve guide in the rat. Plastic and Reconstructive Surgery, 78(6), 793–800.
63.
SembaK., EggerM.D. (1986). The facial “motor” nerve of the rat: Control of vibrissal movement and examination of motor and sensory components. The Journal of Comparative Neurology, 247(2), 144–158.
64.
SembaK., SzechtmanH., KomisarukB.R. (1980). Synchrony among rhythmical facial tremor, neocortical ‘alpha’ waves, and thalamic non-sensory neuronal bursts in intact awake rats. Brain Research, 195(2), 281–298.
65.
SkourasE., OzsoyU., SarikciogluL., AngelovD.N. (2011). Intrinsic and therapeutic factors determining the recovery of motor function after peripheral nerve transection. Annals of Anatomy, 193(4), 286–303.
66.
SonY.J., TrachtenbergJ.T., ThompsonW.J. (1996). Schwann cells induce and guide sprouting and reinnervation of neuromuscular junctions. Trends in Neurosciences, 19(7), 280–285.
67.
SpectorJ.G., LeeP., DerbyA., RoufaD.G. (1995). Comparison of rabbit facial nerve regeneration in nerve growth factor-containing silicone tubes to that in autologous neural grafts. Annals of Otology, Rhinology, and Laryngology, 104(11), 875–885.
68.
SunK., ZhangJ., ChenT., ChenZ., ChenZ., LiZ., LiH., HuP. (2009). Three-dimensional reconstruction and visualization of the median nerve from serial tissue sections. Microsurgery, 29(7), 573–577.
69.
TamS.L., GordonT. (2003). Mechanisms controlling axonal sprouting at the neuromuscular junction. Journal of Neurocytology, 32(5-8), 961–974.
70.
TomitaK., KuboT., MatsudaK., YanoK., TohyamaM., HosokawaK. (2007). Myelin-associated glycoprotein reduces axonal branching and enhances functional recovery after sciatic nerve transection in rats. Glia, 55(14), 1498–1507.
71.
TomovT.L., Guntinas-LichiusO., GroshevaM., StreppelM., SchraermeyerU., NeissW.F., AngelovD.N. (2002). An example of neural plasticity evoked by putative behavioral demand and early use of vibrissal hairs after facial nerve transection. Experimental Neurology, 178(2), 207–218.
72.
TrojanD.A., GendronD., CashmanN.R. (1991). Electrophysiology and electrodiagnosis of the post-polio motor unit. Orthopedics, 14(12), 1353–1361.
73.
WeissP. (1944). The technology of nerve regeneration: A review. Sutureless tubulation and related methods of nerve repair. Journal of Neurosurgery, 1(6), 400–450.
74.
WeissP., HoagA. (1946). Competitive reinnervation of rat muscles by their own and foreign nerves. Journal of Neurophysiology, 9, 413–418.
75.
WeissP., TaylorA.C. (1943). Histomechanical analysis of nerve reunion in the rat after tubular splicing. Archives of Surgery, 47(5), 419–447.
76.
WeissP., TaylorC. (1944). Further experimental evidence against “neurotropism” in nerve regeneration. Journal of Experimental Zoology, 95(2), 233–257.
77.
WelkerW.I. (1964). Analysis of sniffing of the albino rat. Behaviour, 22(3), 223–244.
78.
WilliamsL.R. (1987). Rat aorta isografts possess nerve regeneration-promoting properties in silicone Y chambers. Experimental Neurology, 97(3), 555–563.
79.
WineskiL.E. (1985). Facial morphology and vibrissal movement in the golden hamster. Journal of Morphology, 183(2), 199–217.
