Download PDF
J Reconstr Microsurg 2010; 26(2): 123-129
DOI: 10.1055/s-0029-1243297
© Thieme Medical Publishers

Allografting Combined with Systemic FK506 Produces Greater Functional Recovery than Conduit Implantation in a Rat Model of Sciatic Nerve Injury

Jan Rustemeyer1 , 2 , Ursula Dicke2
  • 1Medical Center Clinic, CMFS, Neuroscience, Bremen, Germany
  • 2University of Bremen, Neuroscience, Bremen, Germany
Further Information

Publication History

Publication Date:
10 December 2009 (online)

    Permissions and Reprints

ABSTRACT

Implantation of allografts or nerve conduits has been used to promote regeneration following peripheral nerve injuries involving substantial axon loss. Both methods provide promising alternatives to autologous grafting and avoid donor site morbidity. We compared the relative efficacies of allografting versus conduit implantation in a rat model of sciatic nerve regeneration. Two rat strains (Lewis and Dark Agouti; n = 30) were employed. Unoperated animals served as controls (group I). Animals in groups II and III underwent left sciatic nerve resection over a distance of 15 mm; group II animals received implants of collagen type I conduits; and group III animals received allografts from the other rat strain and systemic low-dose (0.1 mg/kg/d) administration of FK506. Walking tracks were recorded after 4, 8, 12, and 16 weeks; nerve sections were stained for myelin basic protein after 16 weeks. Functional tests revealed significantly better recovery in group III animals compared with group II even though there was no significant difference in the extent of remyelination. Neither group achieved the functional or histomorphometric values of control animals. Improved functional recovery following allografting plus systemic FK506, in comparison with conduit implantation, underlines the importance of systemic administration of neurotrophic molecules for nerve regeneration.

KEYWORDS

Sciatic nerve repair - allograft nerve transplantation - FK506 - nerve conduit - nerve regeneration

REFERENCES

  • 1 Ortigüela M E, Wood M B, Cahill D R. Anatomy of the sural nerve complex.  J Hand Surg [Am]. 1987;  12 1119-1123
    PubMedGoogle Scholar
  • 2 Rappaport W D, Valente J, Hunter G C et al.. Clinical utilization and complications of sural nerve biopsy.  Am J Surg. 1993;  166 252-256
    CrossrefPubMedGoogle Scholar
  • 3 Kumar P A, Hassan K M. Cross-face nerve graft with free-muscle transfer for reanimation of the paralyzed face: a comparative study of the single-stage and two-stage procedures.  Plast Reconstr Surg. 2002;  109 451-462 discussion 463-464
    CrossrefPubMedGoogle Scholar
  • 4 Udina E, Ceballos D, Verdú E, Gold B G, Navarro X. Bimodal dose-dependence of FK506 on the rate of axonal regeneration in mouse peripheral nerve.  Muscle Nerve. 2002;  26 348-355
    CrossrefPubMedGoogle Scholar
  • 5 Hontanilla B, Aubá C, Arcocha J, Gorría O. Nerve regeneration through nerve autografts and cold preserved allografts using tacrolimus (FK506) in a facial paralysis model: a topographical and neurophysiological study in monkeys.  Neurosurgery. 2006;  58 768-779 discussion 768-779
    CrossrefPubMedGoogle Scholar
  • 6 Mackinnon S E, Doolabh V B, Novak C B, Trulock E P. Clinical outcome following nerve allograft transplantation.  Plast Reconstr Surg. 2001;  107 1419-1429
    CrossrefPubMedGoogle Scholar
  • 7 Song Y X, Muramatsu K, Kurokawa Y et al.. Functional recovery of rat hind-limb allografts.  J Reconstr Microsurg. 2005;  21 471-476
    Article in Thieme ConnectPubMedGoogle Scholar
  • 8 Haisheng H, Songjie Z, Xin L. Assessment of nerve regeneration across nerve allografts treated with tacrolimus.  Artif Cells Blood Substit Immobil Biotechnol. 2008;  36 465-474
    CrossrefPubMedGoogle Scholar
  • 9 Chen B, Song Y, Liu Z. Promotion of nerve regeneration in peripheral nerve by short-course FK506 after end-to-side neurorrhaphy.  J Surg Res. 2009;  152 303-310
    CrossrefPubMedGoogle Scholar
  • 10 Chabas J F, Alluin O, Rao G et al.. FK506 induces changes in muscle properties and promotes metabosensitive nerve fiber regeneration.  J Neurotrauma. 2009;  26 97-108
    CrossrefPubMedGoogle Scholar
  • 11 Archibald S J, Shefner J, Krarup C, Madison R D. Monkey median nerve repaired by nerve graft or collagen nerve guide tube.  J Neurosci. 1995;  15(5 Pt 2) 4109-4123
    PubMedGoogle Scholar
  • 12 Hadlock T, Elisseeff J, Langer R, Vacanti J, Cheney M. A tissue-engineered conduit for peripheral nerve repair.  Arch Otolaryngol Head Neck Surg. 1998;  124 1081-1086
    CrossrefPubMedGoogle Scholar
  • 13 Evans G R, Brandt K, Widmer M S et al.. In vivo evaluation of poly(L-lactic acid) porous conduits for peripheral nerve regeneration.  Biomaterials. 1999;  20 1109-1115
    CrossrefPubMedGoogle Scholar
  • 14 Krarup C, Archibald S J, Madison R D. Factors that influence peripheral nerve regeneration: an electrophysiological study of the monkey median nerve.  Ann Neurol. 2002;  51 69-81
    CrossrefPubMedGoogle Scholar
  • 15 Lee D Y, Choi B H, Park J H et al.. Nerve regeneration with the use of a poly(l-lactide-co-glycolic acid)-coated collagen tube filled with collagen gel.  J Craniomaxillofac Surg. 2006;  34 50-56
    PubMedGoogle Scholar
  • 16 Rosson G D, Williams E H, Dellon A L. Motor nerve regeneration across a conduit.  Microsurgery. 2009;  29 107-114
    CrossrefPubMedGoogle Scholar
  • 17 de Medinaceli L, Freed W J, Wyatt R J. An index of the functional condition of rat sciatic nerve based on measurements made from walking tracks.  Exp Neurol. 1982;  77 634-643
    CrossrefPubMedGoogle Scholar
  • 18 Lin F M, Pan Y C, Hom C, Sabbahi M, Shenaq S. Ankle stance angle: a functional index for the evaluation of sciatic nerve recovery after complete transection.  J Reconstr Microsurg. 1996;  12 173-177
    Article in Thieme ConnectPubMedGoogle Scholar
  • 19 Martenson R E. Myelin basic protein speciation.  Prog Clin Biol Res. 1984;  146 511-521
    PubMedGoogle Scholar
  • 20 Greenfield S, Weise M J, Gantt G, Hogan E L, Brostoff S W. Basic proteins of rodent peripheral nerve myelin: immunochemical identification of the 21.5K, 18.5K, 17K, 14K, and P2 proteins.  J Neurochem. 1982;  39 1278-1282
    CrossrefPubMedGoogle Scholar
  • 21 Groome N, Dawkes A, Barry R, Hruby S, Alvord Jr E. New monoclonal antibodies reactive with defined sequential epitopes in human myelin basic protein.  J Neuroimmunol. 1988;  19 305-315
    CrossrefPubMedGoogle Scholar
  • 22 Gold B G, Gordon H S, Wang M S. Efficacy of delayed or discontinuous FK506 administrations on nerve regeneration in the rat sciatic nerve crush model: lack of evidence for a conditioning lesion-like effect.  Neurosci Lett. 1999;  267 33-36
    CrossrefPubMedGoogle Scholar
  • 23 Scipio F D, Raimondo S, Tos P, Geuna S. A simple protocol for paraffin-embedded myelin sheath staining with osmium tetroxide for light microscope observation.  Microsc Res Tech. 2008;  71 497-502
    CrossrefPubMedGoogle Scholar
  • 24 McNulty P A, Macefield V G. Intraneural microstimulation of motor axons in the study of human single motor units.  Muscle Nerve. 2005;  32 119-139
    CrossrefPubMedGoogle Scholar
  • 25 Koob J W, Moradzadeh A, Tong A et al.. Induction of regional collateral sprouting following muscle denervation.  Laryngoscope. 2007;  117 1735-1740
    CrossrefPubMedGoogle Scholar
  • 26 Miyasaka T, Naito A, Shindo M et al.. Modulation of brachioradialis motoneuron excitabilities by group I fibers of the median nerve in humans.  Tohoku J Exp Med. 2007;  212 115-131
    CrossrefPubMedGoogle Scholar
  • 27 Udina E, Ceballos D, Gold B G, Navarro X. FK506 enhances reinnervation by regeneration and by collateral sprouting of peripheral nerve fibers.  Exp Neurol. 2003;  183 220-231
    CrossrefPubMedGoogle Scholar
  • 28 Rustemeyer J, Krajacic A, Dicke U. Histomorphological and functional impacts of postoperative motor training in rats after allograft sciatic nerve transplantation under low-dose FK 506.  Muscle Nerve. 2009;  39 480-488
    CrossrefPubMedGoogle Scholar
  • 29 Meek M F, Den Dunnen W F, Schakenraad J M, Robinson P H. Long-term evaluation of functional nerve recovery after reconstruction with a thin-walled biodegradable poly (DL-lactide-epsilon-caprolactone) nerve guide, using walking track analysis and electrostimulation tests.  Microsurgery. 1999;  19 247-253
    CrossrefPubMedGoogle Scholar
  • 30 Varejão A S, Melo-Pinto P, Meek M F, Filipe V M, Bulas-Cruz J. Methods for the experimental functional assessment of rat sciatic nerve regeneration.  Neurol Res. 2004;  26 186-194
    CrossrefPubMedGoogle Scholar
  • 31 Brushart T M, Mathur V, Sood R, Koschorke G M, Joseph H. Boyes Award. Dispersion of regenerating axons across enclosed neural gaps.  J Hand Surg [Am]. 1995;  20 557-564
    PubMedGoogle Scholar
  • 32 Tomita K, Kubo T, Matsuda K et al.. Effect of conduit repair on aberrant motor axon growth within the nerve graft in rats.  Microsurgery. 2007;  27 500-509
    CrossrefPubMedGoogle Scholar
  • 33 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. 2008;  185 469-483
    CrossrefPubMedGoogle Scholar
  • 34 Pavlov S P, Grosheva M, Streppel M et al.. Manually-stimulated recovery of motor function after facial nerve injury requires intact sensory input.  Exp Neurol. 2008;  211 292-300
    CrossrefPubMedGoogle Scholar
  • 35 Udina E, Gold B G, Navarro X. Comparison of continuous and discontinuous FK506 administration on autograft or allograft repair of sciatic nerve resection.  Muscle Nerve. 2004;  29 812-822
    CrossrefPubMedGoogle Scholar
  • 36 Neuhaus P, McMaster P, Calne R et al.. Neurological complications in the European multicentre study of FK 506 and cyclosporin in primary liver transplantation.  Transpl Int. 1994;  7(Suppl 1) S27-S31
    PubMedGoogle Scholar
  • 37 Rifai K, Klempnauer J, Manns M P, Trassburg C P. Sudden hearing loss associated with high levels of calcineurin inhibitors after liver transplantation.  Transplantationsmedizin. 2006;  18 33-35
    PubMedGoogle Scholar
  • 38 Wang M S, Zeleny-Pooley M, Gold B G. Comparative dose-dependence study of FK506 and cyclosporin A on the rate of axonal regeneration in the rat sciatic nerve.  J Pharmacol Exp Ther. 1997;  282 1084-1093
    PubMedGoogle Scholar
  • 39 Günther E, Walter L. The major histocompatibility complex of the rat (Rattus norvegicus).  Immunogenetics. 2001;  53 520-542
    CrossrefPubMedGoogle Scholar
  • 40 Rustemeyer J, Dicke U. Correlation of three sciatic functional indices with histomorphometric findings in a rat sciatic nerve allograft repair model.  Microsurgery. 2009;  29(7) 560-567
    CrossrefPubMedGoogle Scholar
  • 41 Katsube K, Doi K, Fukumoto T, Fujikura Y, Shigetomi M, Kawai S. Successful nerve regeneration and persistence of donor cells after a limited course of immunosuppression in rat peripheral nerve allografts.  Transplantation. 1998;  66 772-777
    CrossrefPubMedGoogle Scholar
  • 42 Keilhoff G, Fansa H, Schneider W, Wolf G. In vivo predegeneration of peripheral nerves: an effective technique to obtain activated Schwann cells for nerve conduits.  J Neurosci Methods. 1999;  89 17-24
    CrossrefPubMedGoogle Scholar
  • 43 Kalbermatten D F, Erba P, Mahay D, Wiberg M, Pierer G, Terenghi G. Schwann cell strip for peripheral nerve repair.  J Hand Surg Eur Vol. 2008;  33 587-594
    PubMedGoogle Scholar
  • 44 Tohill M, Terenghi G. Stem-cell plasticity and therapy for injuries of the peripheral nervous system.  Biotechnol Appl Biochem. 2004;  40(Pt 1) 17-24
    CrossrefPubMedGoogle Scholar
  • 45 Chen C J, Ou Y C, Liao S L et al.. Transplantation of bone marrow stromal cells for peripheral nerve repair.  Exp Neurol. 2007;  204 443-453
    CrossrefPubMedGoogle Scholar
  • 46 Meek M F, Den Dunnen W F. Porosity of the wall of a Neurolac nerve conduit hampers nerve regeneration.  Microsurgery. 2009;  29 473-478
    CrossrefPubMedGoogle Scholar
  • 47 Waitayawinyu T, Parisi D M, Miller B et al.. A comparison of polyglycolic acid versus type 1 collagen bioabsorbable nerve conduits in a rat model: an alternative to autografting.  J Hand Surg [Am]. 2007;  32 1521-1529
    PubMedGoogle Scholar
  • 48 Alluin O, Wittmann C, Marqueste T et al.. Functional recovery after peripheral nerve injury and implantation of a collagen guide.  Biomaterials. 2009;  30 363-373
    CrossrefPubMedGoogle Scholar

Jan Rustemeyer

Medical Center Clinic, CMFS

ST Juergen Str Bremen 28177, Germany

Email: janrustem@gmx.de

      >