Abstract
Transection and re-anastomosis of the purely motor facial nerve leads to poor functional recovery. However, we have recently shown in rat that manual stimulation (MS) of denervated vibrissal muscles reduces the number of polyinnervated motor endplates and promotes full recovery of whisking. Here, we examined whether MS of denervated rat forearm muscles would also improve recovery following transection and suture of the mixed (sensory and motor) median nerve (median–median anastomosis, MMA). Following MMA of the right median nerve, animals received no postoperative treatment, daily MS of the forearm muscles or handling only. An almost identical level of functional recovery, measured by the force of grip in grams, was reached in all animals by the sixth postoperative week and maintained till 3 months following surgery regardless of the postoperative treatment. Also, we found no differences among the groups in the degree of axonal sprouting, the extent of motor endplate polyinnervation and in the soma size of regenerated motoneurons. Taken together, we show that while MS is beneficial following motor nerve injury, combined strategies will be required for functional recovery following mixed nerve injury.
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Abramoff MD, Magelhaes PJ, Ram SJ (2004) Image processing with Image. J Biophotonics Int 11:36–42
Al-Majed AA, Newmann CM, Brushart TM, Gordon T (2000) Brief electrical stimulation promotes the speed and accuracy of motor axonal regeneration. J Neurosci 20:2602–2608
Amr SM, Moharram AN, Abdel-Meguid KM (2006) 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 5:1–6
Angelov DN, Guntinas-Lichius O, Wewetzer K, Neiss WF, Streppel M (2005) Axonal branching and recovery of coordinated muscle activity after transection of the facial nerve in adult rats. Adv Anat Embryol Cell Biol 180:1–130
Angelov DN, Ceynowa M, Guntinas-Lichius O, Streppel M, Grosheva M, Kiryakova SI, Skouras E, Maegele M, Irintchev AP, Neiss WF, Sinis N, Alvanou A, Dunlop SA (2007) Mechanical stimulation of paralyzed vibrissal muscles following facial nerve injury in adult rat promotes full recovery of whisking. Neurobiol Disease 26:229–242
Archibald SJ, Krarup C, Shefner J, Li ST, Madison RD (1991) A collagen based nerve guide conduit for peripheral nerve repair: an electrophysiological study of nerve regeneration in rodents and non-human primates. J Comp Neurol 306:685–696
Archibald SJ, Shefner J, Krarup C, Madison RD (1995) Monkey median nerve repaired by nerve graft or collagen nerve guide tube. J Neurosci 15:4109–4123
Barry JA, Ribchester RR (1995) Persistent polyneuronal innervation in partially denervated rat muscle after reinnervation and recovery from prolonged nerve conduction block. J Neurosci 15:6327–6339
Bertelli JA, Mira JC (1995) The grasping test: a simple behavioral method for objective quantitative assessment of peripheral nerve regeneration in the rat. J Neurosci Methods 58:151–155
Björkman A, Rosen B, Lundborg G (2005) Anaesthesia of the axillary plexus induces rapid improvement of sensory function in the contralateral hand: an effect of interhemispheric plasticity. Scand J Plast Reconstr Surg Hand Surg 39:234–237
Blanco JE, Anderson KD, Steward O (2007) Recovery of forepaw gripping ability and reorganization of cortical motor control following cervical spinal cord injuries in mice. Exp Neurol 203:333–348
Blinzinger K, Kreutzberg G (1968) Displacement of synaptic terminals from regenerating motoneurons by microglial cells. Z Zellforsch Mikrosk Anat 85:145–157
Bontioti EN, Kanje M, Dahlin LB (2003) Regeneration and functional recovery in the upper extremity of rats after various types of nerve injuries. J Peripher Nerv Syst 8:159–168
Bontioti E, Kanje M, Lundborg G, Dahlin LB (2005) End-to-side nerve repair in the upper extremity of rat. J Peripher Nerv Syst 10:58–68
Brännström T, Kellerth JO (1998) Changes in synaptology of adult cat spinal alpha-motoneurons after axotomy. Exp Brain Res 118:1–13
Brännström T, Kellerth JO (1999) Recovery of synapses in axotomized adult cat spinal motoneurons after reinnervation into muscle. Exp Brain Res 125:19–27
Brännström T, Havton L, Kellerth JO (1992a) Changes in size and dendritic arborization patterns of adult cat spinal alpha-motoneurons following permanent axotomy. J Comp Neurol 318:439–451
Brännström T, Havton L, Kellerth JO (1992b) Restorative effects of reinnervation on the size and dendritic arborization patterns of axotomized cat spinal alpha-motoneurons. J Comp Neurol 318:452–461
Brown MC, Holland RL, Hopkins WG, Keynes RJ (1981) An assessment of the spread of the signal for terminal sprouting within and between muscles. Brain Res 210:145–151
Cangiano A, Magherini PC, Pasino E, Pellegrino M, Risaliti R (1984) Interaction of inactivity and nerve breakdown products in the origin of acute denervation changes in rat skeletal muscle. J Physiol 355:3435–3465
Chen R, Cohen LG, Hallett M (2002) Nervous system reorganization following injury. Neuroscience 111:761–773
Choi D, Raisman G (2005) Disorganization of the facial nucleus after nerve lesioning and regeneration in the rat: effects of transplanting candidate reparative cells to the site of injury. Neurosurgery 56:1093–1100
Dickens P, Hill P, Bennett MR (2003) Schwann cell dynamics with respect to newly formed motor-nerve terminal branches on mature (Bufo marinus) muscle fibers. J Neurocytol 32:381–392
Dillon D, Gibbs MA, Baby C (2007) Peripheral nerve blocks of the hand. Acad Emerg Med 14:14–15
Dörfl J (1982) The musculature of the mystacial vibrissae of the white mouse. J Anat 135:147–154
Dohm S, Streppel M, Guntinas-Lichius O, Pesheva P, Probstmeier R, Walther M, Neiss WF, Stennert E, Angelov DN (2000) Local application of extracellular matrix proteins fail top reduce the number of axonal branches after varying reconstructive surgery on rat facial nerve. Restor Neurol Neurosci 16:117–126
Dumont CE, Alnot JY (1998) Proximal median and ulnar resections. Results of primary and secondary repairs. Rev Chir Orthop Reparatrice Appar Mot 84:590–599
Evgenieva E, Schweigert P, Guntinas-Lichius O, Grosheva M, Angelova SK, Streppel M, Irintchev A, Skouras E, Sinis N, Dunlop SA, Radeva V, Angelov DN (2007) Mechanical stimulation of tongue muscles diminishes polynnervation of the motor end-plates and improves recovery of function after hypoglossal nerve injury in rats (submitted)
Florence SL, Garraghty PE, Wall JT, Kaas JH (1994) Sensory afferent projections and area 3b somatotopy following median nerve cut and repair in macaque monkeys. Cereb Cortex 4:391–407
Galtrey CM, Asher RA, Nothias F, Fawcett JW (2007) Promoting plasticity in the spinal cord with chondroitinase improves functional recovery after peripheral nerve repair. Brain 130:926–939
Gordon T, Hegedus J, Tam SL (2004) Adaptive and maladaptive motor axonal sprouting in aging and motoneuron disease. Neurol Res 26:174–185
Gorio A, Carmignoto G, Finesso M, Polato P, Nunzi MG (1983) Muscle reinnervation. II. Sprouting, synapse formation and repression. Neuroscience 8:403–416
Greene EC (1935) Anatomy of the rat. Transactions of the American Philosophical Society, Philadelphia, New Series, Volume XXVII, 1935
Grimby G, Einarsson G, Hedberg M, Aniansson A (1989) Muscle adaptive changes in post-polio subjects. Scand J Rehabil Med 21:19–26
Gundersen HJ (1986) Stereology of arbitrary particles. J Microsc 143:3–45
Guntinas-Lichius O, Angelov DN, Tomov TL, Dramiga J, Neiss WF, Wewetzer K (2001) Transplantation of olfactory ensheathing cells stimulates the collateral sprouting from axotomized adult rat facial motoneurons. Exp Neurol 172:70–80
Guntinas-Lichius O, Angelov DN, Morellini F, Lenzen M, Skouras E, Schachner M, Irintchev A (2005a) Opposite impacts of tenascin-C and tenascin-R deficiency in mice on the functional outcome of facial nerve repair. Eur J Neurosci 22:2171–2179
Guntinas-Lichius O, Irintchev A, Streppel M, Lenzen M, Grosheva M, Wewetzer K, Neiss WF, Angelov DN (2005b) Factors limiting motor recovery after facial nerve transection in the rat: combined structural and functional analyses. Eur J Neurosci 21:391–402
Guntinas-Lichius O, Hundeshagen G, Paling T, Streppel M, Grosheva M, Irintchev AP, Skouras A, Alvanou A, Angelova SK, Kuerten S, Sinis N, Dunlop SA, Angelov DN (2007) Manual stimulation of facial muscles improves functional recovery after hypoglossal-facial anastomosis and interpositional nerve grafting of the facial nerve in adult rats. Neurobiol Disease, accepted for press on 02.07.2007
Hall S (2005) The response to injury in the peripheral nervous system. J Bone Joint Surg 87B:1309–1319
Hansson T, Brismar T (2003) Loss of sensory discrimination after median nerve injury and activation in the primary somatosensory cortex on functional magnetic resonance imaging. J Neurosurg 99:100–105
Ito M, Kudo M (1994) Reinnervation by axon collaterals from single facial motoneurons to multiple targets following axotomy in the adult guinea pig. Acta Anat 151:124–130
Kelly EJ, Jacoby C, Terenghi G, Mennen U, Ljungberg C, Wiberg M (2007) End-to-side nerve coaptation: a qualitative and quantitative assessment in the primate. J Plast Reconstr Aesthet Surg 60:1–12
Klein BG, Rhoades RW (1985) Representation of whisker follicle intrinsic musculature in the facial motor nucleus of the rat. J Comp Neurol 232:55–69
Krarup C, Archibald SJ, Madison RD (2002) Factors that influence peripheral nerve regeneration: an electrophysiological study of the monkey median nerve. Ann Neurol 51:69–81
Love FM, Son YJ, Thompson WJ (2003) Activity alters muscle reinnervation and terminal sprouting by reducing the number of Schwann cell pathways that grow to link synaptic sites. J Neurobiol 54:566–576
Lowe AA (1981) The neural regulation of tongue movements. Progr Neurobiol 15:295–344
Lowe BD, Freivalds A (1999) Effect of carpal tunnel syndrome on grip force coordination on hand tools. Ergonomics 42:550–564
Lundborg G (2005) Nerve injury and repair. Churchill Livingstone, Edinburgh
Lundborg G, Rosen B (2007) Hand function after nerve repair. Acta Physiol 189:207–217
Lundborg G, Björkman A, Hansson T, Nylander L, Nyman T, Rosen B (2005) Artificial sensibility of the hand based on cortical audiotactile interaction: a study using functional magnetic resonance imaging. Scand J Plast Reconstr Surg Hand Surg 39:370–372
Mackinnon SE, Dellon AL, Hudson AR, Hunter DA (1985) A primate model for chronic nerve compression. J Reconstr Microsurg 1:185–195
Madison RD, Archibald SJ, Lacin R, Krarup C (1999) Factors contributing to preferential motor reinnervation in the primate peripheral nervous system. J Neurosci 19:11007–11016
Mailander P, Berger A, Schaller E, Ruhe K (1989) Results of primary nerve repair in the upper extremity. Microsurgery 10:147–150
McPhail LT, Fernandes KJ, Chan CC, Vanderluit JL, Tetzlaff W (2004) Axonal reinjury reveals the survival and re-expression of regeneration-associated genes in chronically axotomized adult mouse motoneurons. Exp Neurol 188:331–340
Midha R (2006) Emerging techniques for nerve repair: nerve transfers and nerve guidance tubes. Clin Neurosurg 53:185–190
Morris J, Hudson AR, Weddell G (1972) Study of degeneration and regeneration in the divided rat sciatic nerve based on electron microscopy. II. The development of the “regenerating unit”. Z Zellforsch mikrosk Anat 124:103–130
Neiss WF, Guntinas-Lichius O, Angelov DN, Gunkel A, Stennert E (1992) The hypoglossal-facial anastomosis as model of neuronal plasticity in the rat. Ann Anat 174:419–433
Nowak DA, Hermsdorfer J (2003) Selective deficits of grip force control during object manipulation in patients with reduced sensibility of the grasping digits. Neurosci Res 47:65–72
O'Reilly PMR, Fitzgerald MJT (1990) Fibre composition of the hypoglossal nerve in the rat. J Anat 172:227–243
Papalia I, Tos P, Stagno d'Alcontres F, Battiston B, Geuna S (2003) On the use of the grasping test in the rat median nerve model: a re-appraisal of its efficacy for quantitative assessment of motor function recovery. J Neurosci Methods 127:43–47
Pockett S, Slack JR (1982) Source of the stimulus for nerve terminal sprouting in partially denervated muscle. Neuroscience 7:3173–3176
Rajan B, Polydefkis M, Hauer P, Griffin JW, McArthur JC (2003) Epidermal reinnervation after intracutaneous axotomy in man. J Comp Neurol 457:24–36
Rathakrishnan R, Therimadasamy AK, Chan YH, Wilder-Smith EP (2007) The median palmar cutaneous nerve in normal subjects and CTS. Clin Neurophysiol 118:776–80
Rich MM, Lichtman JW (1989) In vivo visualization of pre- and postsynaptic change during synapse elimination in reinnervated mouse muscle. J Neurosci 9:1781–1805
Rosen B, Lundborg G (2007) Enhanced sensory recovery after median nerve repair using cortical audio-tactile interaction: a randomised multicentre study. J Hand Surg 32:31–37
Rosen B, Björkman A, Lundborg G (2006) Improved sensory relearning after nerve repair induced by selective temporary anaesthesia: a new concept in hand rehabilitation. J Hand Surg 31B:126–132
Schröder JM (1968) Die Hyperneurotisation Büngnerscher Bänder bei der experimentallen Isoniazid Neuropathie: Phasenkontrast- und elektronenmikroskopische Untersuchungen. Virchows Arch Abt B1:131–156
Segev I (1998) Sound grounds for computing dendrites. Nature 393:207–208
Semba K, Egger MD (1986) The facial “motor” nerve of the rat: control of vibrissal movement and examination of motor and sensory components. J Comp Neurol 247:144–158
Shawe GD (1954) On the number of branches formed by regenerating nerve fibers. Br J Surg 42:474–488
Shieh SJ, Lee JW, Chiu HY (2007) Long-term functional results of primary reconstruction of severe forearm injuries. J Plast Reconstr Aesthet Surg 60:339–348
Sinis N, Schaller HE, Schulte-Eversum C, Schlosshauer B, Doser M, Dietz K, Rosner H, Muller HW, Haerle M (2005) Nerve regeneration across a 2-cm gap in the rat median nerve using a resorbable nerve conduit filled with Schwann cells. J Neurosurg 103:1067–1076
Simova O, Irintchev A, Mehanna A, Liu J, Dihne M, Bahle D, Sewald N, Loers G, Schachner M (2006) Carbohydrate mimics promote functional recovery after peripheral nerve repair. Ann Neurol 60:827–835
Son YJ, Trachtenberg JT, Thompson WJ (1996) Schwann cells induce and guide sprouting and reinnervation of neuromuscular junctions. Trends Neurosci 19:280–285
Spruston N, Schiller Y, Stuart G, Sakmann B (1995) Activity-dependent action potential invasion and calcium influx into hippocampal CA1 dendrites. Science 268:297–300
Standler NA, Bernstein JJ (1982) Degeneration and regeneration of motoneuron dendrites after ventral root crush: computer reconstruction of dendritic fields. Exp Neurol 75:600–615
Streppel M, Azzolin N, Dohm S, Guntinas-Lichius O, Haas C, Grothe C, Neiss WF, Angelov DN (2002) Focal application of neutralizing antibodies to soluble neurotrophic faactors reduces collateral axonal branching after peripheral nerve lesion. Eur J Neurosci 15:1327–1342
Sulaiman OA, Midha R, Munro CA, Matsuyama T, Al-Majed A, Gordon T (2002) Chronic Schwann cell denervation and the presence of a sensory nerve reduce motor axonal regeneration. Exp Neurol 176:342–354
Sumner BE, Watson WE (1971) Retraction and expansion of the dendritic tree of motor neurones of adult rats induced in vivo. Nature 233:273–275
Tam SL, Gordon T (2003) Mechanisms controlling axonal sprouting at the neuromuscular junction. J Neurocytol 32:961–974
Tang XQ, Heron P, Mashburn C, Smith GM (2007) Targeting sensory axon regeneration in adult spinal cord. Neuroscience 27:6068–6078
Terzis JK, Papakonstantinou KC (2000) The surgical treatment of brachial plexus injuries in adults. Plast Reconstr Surg 106:1097–1122
Thonnard J, Saels P, Van den Bergh P, Lejeune T (1999) Effects of chronic median nerve compression at the wrist on sensation and manual skills. Exp Brain Res 128:61–64
Tolu E, Caria MA, Pugliatti M (1993) Responses of hypoglossal motoneurons to mechanical stimulation of the teeth in rats. Arch Ital Biol 131:191–200
Tomov TL, Guntinas-Lichius O, Grosheva M, Streppel M, Schraermeyer U, Neiss WF, Angelov DN (2002) An example of neural plasticity evoked by putative behavioral demand and early use of vibrissal hairs after facial nerve transection. Exp Neurol 178:207–218
Tos P, Battiston B, Nicolino S, Raimondo S, Fornaro M, Lee JM, Chirila L, Geuna S, Perroteau I (2007) Comparison of fresh and predegenerated muscle-vein-combined guides for the repair of rat median nerve. Microsurgery 27:48–55
Trojan DA, Gendron D, Cashman NR (1991) Electrophysiology and electrodiagnosis of the post-polio motor unit. Orthopedics 14:1353–1361
Tsuboya H, Tani T, Ishida K, Ushida T, Taniguchi S, Kimura J (2007) Quantitative sensory testing of cold and vibration perception during compression of median nerve at the wrist. Muscle Nerve 35:458–464
Tsuyoshi H, Zenzai K, Okado H, Endo N, Shibata M, Hirano S (2006) Sprouting of sensory neurons in dorsal root ganglia after transection of peripheral nerves. Arch Histol Cytol 69:173–179
Valero-Cabre A, Tsironis K, Skouras E, Navarro X, Neiss WF (2004) Peripheral and spinal motor reorganization after nerve injury and repair. J Neurotrauma 21:95–108
Van den Noven S, Wallace N, Muccio D, Turtz A, Pinter MJ (1993) Adult spinal motoneurons remain viable despite prolonged absence of functional synaptic contact with muscle. Exp Neurol 123:147–156
Vetter P, Roth A, Hausser M (2001) Propagation of action potentials in dendrites depends on dendritic morphology. J Neurophysiol 85:926–937
Vordemvenne T, Langer M, Ochman S, Raschke M, Schult M (2007) Long-term results after primary microsurgical repair of ulnar and median nerve injuries: a comparison of common score systems. Clin Neurol Neurosurg 109:263–271
Wall JT, Xu J, Wang X (2002) Human brain plasticity: an emerging view of the multiple substrates and mechanisms that cause cortical changes and related sensory dysfunctions after injuries of sensory inputs from the body. Brain Res Brain Res Rev 39:181–215
Witzel C, Rohde C, Brushart TM (2005) Pathway sampling by regenerating peripheral axons. J Comp Neurol 485:183–190
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The present study was supported by the Jean-Uhrmacher Foundation, Köln Fortune Programm, and the DFG (AN 331/3-1, AN 331/5-1). SAD is a Senior Research Fellow (National Health & Medical Research Council, Australia; grant ID: 254670). The skillful assistance of D. Bösel, D. Felder, N. Lange, C. Backhausen and L. Wilken is highly appreciated.
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S. A. Dunlop and D. N. Angelov contributed equally and share last authorship.
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Sinis, N., Guntinas-Lichius, O., Irintchev, A. et al. Manual stimulation of forearm muscles does not improve recovery of motor function after injury to a mixed peripheral nerve. Exp Brain Res 185, 469–483 (2008). https://doi.org/10.1007/s00221-007-1174-y
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DOI: https://doi.org/10.1007/s00221-007-1174-y