TY  - JOUR
T1  - EFFECT OF FK506 ADMINISTRATION IN ALPHA MOTOR NEURONS AFTER PRIMARY AND DELAYED REPAIR OF THE SCIATIC NERVE
AU  - Özsoy, Umut
AU  - Yıldırım, Fatoş Belgin
AU  - Demirel, Bahadır Murat
AU  - Hızay, Arzu
AU  - Sarıkcıoğlu, Levent
AU  - Demir, Necdet
AU  - Tanrıöver, Gamze
AU  - Süzen, Bikem
AU  - Oğuz, Nurettin
PY  - 2016
DA  - June
JF  - Anatomy
JO  - Anatomy
PB  - Society of Anatomy and Clinical Anatomy
WT  - DergiPark
SN  - 1308-8459
SP  - 30
EP  - 39
VL  - 10
IS  - 1
LA  - en
AB  - Objectives: FK506 is an effective immunosuppressive drug for treating graft rejection in transplants patients. However, theneuroregenerative effect of FK506 has been well described in the literature. The aim of this study was to investigate the effectsof FK506 in alpha motor neurons after primary and delayed repair of sciatic nerve.Methods: Rats (n=72) were divided into 6 groups. Control, sham-operated, primary repair FK506 (-), primary repair FK506(+), delayed repair FK506 (-), and delayed repair FK506 (+) groups.Results: After injury, the normal structure of the motor neuron perikarya was maintained by primary repair in the FK506 (+)group. In the delayed repair group, beneficial effect of FK506 was found to be less effective. The SFI value reached -50 recoverylevel in the FK506-treated group earlier than those of not FK506-treated groups.Conclusion: Beneficial effect of FK506 has been approved by functional and ultrastructural data in both of primary anddelayed repair groups.
KW  - delayed repair
KW  - FK506
KW  - primary repair
KW  - regeneration
KW  - sciatic nerve
CR  - Aldskogius H, Kozlova EN. Central neuron-glial and glial-glial
CR  - interactions following axon injury. Prog Neurobiol 1998;55:1–26.
CR  - Bisby MA, Tetzlaff W. Changes in cytoskeletal protein synthesis following
CR  - axon injury and during axon regeneration. Mol Neurobiol
CR  - ;6:107–23.
CR  - de la Cruz RR, Pastor AM, Delgado-Garcia JM. Influence of the
CR  - postsynaptic target on the functional properties of neurons in the
CR  - adult mammalian central nervous system. Rev Neurosci 1996;7:115–
CR  - Lowrie MB, Vrbova G. Dependence of postnatal motoneurones on
CR  - their targets: review and hypothesis. Trends Neurosci 1992;15:80–4.
CR  - Hefti F. Pharmacology of neurotrophic factors. Annu Rev
CR  - Pharmacol Toxicol 1997;37:239–67.
CR  - Lindsay RM. Neurotrophins and receptors. Prog Brain Res
CR  - ;103:3–14.
CR  - Muller HW. Gene expression in nerve regeneration. Diabet Med
CR  - ;13:682.
CR  - Sendtner M. Neurotrophic factors for experimental treatment of
CR  - motoneuron disease. Prog Brain Res 1996;109:365–71.
CR  - Terenghi G. Peripheral nerve regeneration and neurotrophic factors.
CR  - J Anat 1999;194:1–14.
CR  - Snider WD, Elliott JL, Yan Q. Axotomy-induced neuronal death
CR  - during development. J Neurobiol 1992;23:1231–46.
CR  - Hoffmann CF, Choufoer H, Marani E, Thomeer RT.
CR  - Ultrastructural study on avulsion effects of the cat cervical motoaxonal
CR  - pathways in the spinal cord. Clin Neurol Neurosurg 1993;95:
CR  - S39–47.
CR  - Martin LJ, Kaiser A, Price AC. Motor neuron degeneration after sciatic
CR  - nerve avulsion in adult rat evolves with oxidative stress and is
CR  - apoptosis. J Neurobiol 1999;40:185–201.
CR  - Novikov L, Novikova L, Kellerth JO. Brain-derived neurotrophic
CR  - factor promotes survival and blocks nitric oxide synthase expression
CR  - in adult rat spinal motoneurons after ventral root avulsion. Neurosci
CR  - Lett 1995;200:45–8.
CR  - Wu W. Expression of nitric-oxide synthase (NOS) in injured CNS
CR  - neurons as shown by NADPH diaphorase histochemistry. Exp
CR  - Neurol 1993;120:153–9.
CR  - Tandrup T, Woolf CJ, Coggeshall RE. Delayed loss of small dorsal
CR  - root ganglion cells after transection of the rat sciatic nerve. J Comp
CR  - Neurol 2000;422:172–80.
CR  - Johnson IP, Duberley RM. Motoneuron survival and expression of
CR  - neuropeptides and neurotrophic factor receptors following axotomy
CR  - in adult and ageing rats. Neuroscience 1998;84:141–50.
CR  - Mattsson P, Meijer B, Svensson M. Extensive neuronal cell death
CR  - following intracranial transection of the facial nerve in the adult rat.
CR  - Brain Res Bull 1999;49:333–41.
CR  - Tornqvist E, Aldskogius H. Motoneuron survival is not affected by
CR  - the proximo-distal level of axotomy but by the possibility of regenerating
CR  - axons to gain access to the distal nerve stump. J Neurosci Res
CR  - ;39:159–65.
CR  - Yu WH. Regulation of nitric oxide synthase expression in motoneurons
CR  - following nerve injury. Dev Neurosci 1997;19:247–54.
CR  - Arvidsson J, Aldskogius H. Effect of repeated hypoglossal nerve
CR  - lesions on the number of neurons in the hypoglossal nucleus of adult
CR  - rats. Exp Neurol 1982;75:520–4.
CR  - Crews LL, Wigston DJ. The dependence of motoneurons on their
CR  - target muscle during postnatal development of the mouse. J
CR  - Neurosci 1990;10:1643–53.
CR  - Johnson IP, Sears TA, Hunter AS. Retrograde response to axotomy
CR  - of motoneurons in the thoracic spinal cord of the aging cat.
CR  - Neurobiol Aging 1991;12:151–60.
CR  - Kuzis K, Coffin JD, Eckenstein FP. Time course and age dependence
CR  - of motor neuron death following facial nerve crush injury: role
CR  - of fibroblast growth factor. Exp Neurol 1999;157:77–87.
CR  - Anneser JM, Berthele A, Borasio GD, Castro-Lopes JM,
CR  - Zieglgansberger W, Tolle TR. Axotomy of the sciatic nerve differentially
CR  - affects expression of metabotropic glutamate receptor
CR  - mRNA in adult rat motoneurons. Brain Res 2000;868:215–21.
CR  - Vanden Noven S, Wallace N, Muccio D, Turtz A, Pinter MJ. Adult
CR  - spinal motoneurons remain viable despite prolonged absence of
CR  - functional synaptic contact with muscle. Exp Neurol 1993;123:147–
CR  - Kim HS, Park YI. Isolation and identification of a novel microorganism
CR  - producing the immunosuppressant tacrolimus. J Biosci
CR  - Bioeng 2008;105:418–21.
CR  - Abraham RT, Wiederrecht GJ. Immunopharmacology of
CR  - rapamycin. Annu Rev Immunol 1996;14:483–510.
CR  - Dumont FJ, Ok H, Lin S, Kastner CA, Cryan J, Martin MM,
CR  - Wiederrecht G, Staruch MJ. Mixed agonist/antagonist activity of an
CR  - FK-506-related immunosuppressant: biological and biochemical
CR  - characterization. J Pharmacol Exp Ther 1996;276:1078–88.
CR  - Brenner MJ, Fox IK, Kawamura DH, Yu VM, Lowe JB 3rd, Hunter
CR  - DA, Mackinnon SE. Delayed nerve repair is associated with diminished
CR  - neuroenhancement by FK506. Laryngoscope 2004;114:570–6.
CR  - Costantini LC, Chaturvedi P, Armistead DM, McCaffrey PG,
CR  - Deacon TW, Isacson O. A novel immunophilin ligand: distinct
CR  - branching effects on dopaminergic neurons in culture and neurotrophic actions after oral administration in an animal model of
CR  - Parkinson's disease. Neurobiol Dis 1998;5:97–106.
CR  - Arii T, Kamiya T, Arii K, Ueda M, Nito C, Katsura KI, Katayama
CR  - Y. Neuroprotective effect of immunosuppressant FK506 in transient
CR  - focal ischemia in rat: therapeutic time window for FK506 in transient
CR  - focal ischemia. Neurol Res 2001;23:755–60.
CR  - Ebisu T, Katsuta K, Fujikawa A, Aoki I, Umeda M, Naruse S,
CR  - Tanaka C. Early and delayed neuroprotective effects of FK506 on
CR  - experimental focal ischemia quantitatively assessed by diffusionweighted
CR  - MRI. Magn Reson Imaging 2001;19:153–60.
CR  - Sharkey J, Butcher SP. Immunophilins mediate the neuroprotective
CR  - effects of FK506 in focal cerebral ischaemia. Nature 1994;371:336–9.
CR  - Bavetta S, Hamlyn PJ, Burnstock G, Lieberman AR, Anderson PN.
CR  - The effects of FK506 on dorsal column axons following spinal cord
CR  - injury in adult rats: neuroprotection and local regeneration. Exp
CR  - Neurol 1999;158:382–93.
CR  - Madsen JR, MacDonald P, Irwin N, Goldberg DE, Yao GL, Meiri
CR  - KF, Rimm IJ, Stieg PE, Benowitz LI. Tacrolimus (FK506) increases
CR  - neuronal expression of GAP-43 and improves functional recovery
CR  - after spinal cord injury in rats. Exp Neurol 1998;154:673–83.
CR  - Gold BG, Yew JY, Zeleny-Pooley M. The immunosuppressant
CR  - FK506 increases GAP-43 mRNA levels in axotomized sensory neurons.
CR  - Neurosci Lett 1998;241:25–8.
CR  - Lyons WE, George EB, Dawson TM, Steiner JP, Snyder SH.
CR  - Immunosuppressant FK506 promotes neurite outgrowth in cultures
CR  - of PC12 cells and sensory ganglia. Proc Natl Acad Sci USA
CR  - ;91:3191–5.
CR  - Gold BG, Gordon HS, Wang MS. Efficacy of delayed or discontinuous
CR  - FK506 administrations on nerve regeneration in the rat sciatic
CR  - nerve crush model: lack of evidence for a conditioning lesion-like
CR  - effect. Neurosci Lett 1999;267:33–6.
CR  - Gold BG, Katoh K, Storm-Dickerson T. The immunosuppressant
CR  - FK506 increases the rate of axonal regeneration in rat sciatic nerve.
CR  - J Neurosci 1995;15:7509–16.
CR  - Lee M, Doolabh VB, Mackinnon SE, Jost S. FK506 promotes functional
CR  - recovery in crushed rat sciatic nerve. Muscle Nerve
CR  - ;23:633–40.
CR  - Wang MS, Zeleny-Pooley M, Gold BG. Comparative dose-dependence
CR  - study of FK506 and cyclosporin A on the rate of axonal regeneration
CR  - in the rat sciatic nerve. J Pharmacol Exp Ther 1997;282:
CR  - –93.
CR  - Navarro X, Udina E, Ceballos D, Gold BG. Effects of FK506 on
CR  - nerve regeneration and reinnervation after graft or tube repair of
CR  - long nerve gaps. Muscle Nerve 2001;24:905–15.
CR  - Sarikcioglu L, Duygulu E, Aydin H, Gurer EI, Ozkan O, Tuzuner
CR  - S. Effects of intrathecal administration of FK506 after sciatic nerve
CR  - crush injury. J Reconstr Microsurg 2006;22:649–54.
CR  - Sobol JB, Lowe IJ, Yang RK, Sen SK, Hunter DA, Mackinnon SE.
CR  - Effects of delaying FK506 administration on neuroregeneration in a
CR  - rodent model. J Reconstr Microsurg 2003;19:113–8.
CR  - Chunasuwankul R, Ayrout C, Dereli Z, Gal A, Lanzetta M, Owen E.
CR  - Low dose discontinued FK506 treatment enhances peripheral nerve
CR  - regeneration. Int Surg 2002;87:274–8.
CR  - Jost SC, Doolabh VB, Mackinnon SE, Lee M, Hunter D.
CR  - Acceleration of peripheral nerve regeneration following FK506
CR  - administration. Restor Neurol Neurosci 2000;17:39–44.
CR  - Sulaiman OA, Midha R, Munro CA, Matsuyama T, Al-Majed A,
CR  - Gordon T. Chronic Schwann cell denervation and the presence of a
CR  - sensory nerve reduce motor axonal regeneration. Exp Neurol
CR  - ;176:342–54.
CR  - Sulaiman OA, Voda J, Gold BG, Gordon T. FK506 increases
CR  - peripheral nerve regeneration after chronic axotomy but not after
CR  - chronic schwann cell denervation. Exp Neurol 2002;175:127–37.
CR  - Pockett S, Gavin RM. Acceleration of peripheral nerve regeneration
CR  - after crush injury in rat. Neurosci Lett 1985;59:221–4.
CR  - Doolabh VB, Mackinnon SE. FK506 accelerates functional recovery
CR  - following nerve grafting in a rat model. Plast Reconstr Surg 1999;
CR  - :1928–36.
CR  - Fansa H, Keilhoff G, Altmann S, Plogmeier K, Wolf G, Schneider
CR  - W. The effect of the immunosuppressant FK 506 on peripheral
CR  - nerve regeneration following nerve grafting. J Hand Surg Br 1999;
CR  - :38–42.
CR  - Yang RK, Lowe JB, 3rd, Sobol JB, Sen SK, Hunter DA, Mackinnon
CR  - SE. Dose-dependent effects of FK506 on neuroregeneration in a rat
CR  - model. Plast Reconstr Surg 2003;112:1832–40.
CR  - Buttemeyer R, Rao U, Jones NF. Peripheral nerve allograft transplantation
CR  - with FK506: functional, histological, and immunological
CR  - results before and after discontinuation of immunosuppression. Ann
CR  - Plast Surg 1995;35:396–401.
CR  - Grand AG, Myckatyn TM, Mackinnon SE, Hunter DA. Axonal
CR  - regeneration after cold preservation of nerve allografts and immunosuppression with tacrolimus in mice. J Neurosurg 2002;96:924–32.
CR  - Weinzweig N, Grindel S, Gonzalez M, Kuy D, Fang J, Shahani B.
CR  - Peripheral-nerve allotransplantation in rats immunosuppressed with
CR  - transient or long-term FK-506. J Reconstr Microsurg 1996;12:451–9.
CR  - Bignotti B, Origo C, Schenone A, Ratto S, Mancardi GL, Ferrari
CR  - ML. Experimental studies on peripheral nerve repair following early
CR  - or delayed suture. Ital J Orthop Traumatol 1986;12:259–66.
CR  - Bolesta MJ, Garrett WE Jr, Ribbeck BM, Glisson RR, Seaber AV,
CR  - Goldner JL. Immediate and delayed neurorrhaphy in a rabbit model:
CR  - a functional, histologic, and biochemical comparison. J Hand Surg
CR  - Am 1988;13:352–7.
CR  - Fu SY, Gordon T. Contributing factors to poor functional recovery
CR  - after delayed nerve repair: prolonged denervation. J Neurosci
CR  - ;15:3886–95.
CR  - Grabb WC. Median and ulnar nerve suture. An experimental study
CR  - comparing primary and secondary repair in monkeys. J Bone Joint
CR  - Surg Am 1968;50:964–72.
CR  - Irintchev A, Draguhn A, Wernig A. Reinnervation and recovery of
CR  - mouse soleus muscle after long-term denervation. Neuroscience
CR  - ;39:231–43.
CR  - Van Beek A, Glover JL, Zook E. Primary versus delayed-primary
CR  - neurorrhaphy in rat sciatic nerve. J Surg Res 1975;18:335–9.
CR  - Wang MS, Gold BG. FK506 increases the regeneration of spinal
CR  - cord axons in a predegenerated peripheral nerve autograft. J Spinal
CR  - Cord Med 1999;22:287–96.
CR  - Kujawa KA, Jones KJ. Testosterone-induced acceleration of recovery
CR  - from facial paralysis in male hamsters: temporal requirements of
CR  - hormone exposure. Physiol Behav 1990;48:765–8.
CR  - Kujawa KA, Kinderman NB, Jones KJ. Testosterone-induced acceleration
CR  - of recovery from facial paralysis following crush axotomy of
CR  - the facial nerve in male hamsters. Exp Neurol 1989;105:80–5.
CR  - de Medinaceli L, Freed WJ, Wyatt RJ. An index of the functional
CR  - condition of rat sciatic nerve based on measurements made from
CR  - walking tracks. Exp Neurol 1982;77:634–43.
CR  - Carlton JM, Goldberg NH. Quantitating integrated muscle function
CR  - following reinnervation. Surg Forum 1986;37:611–2.
CR  - Bain JR, Mackinnon SE, Hunter DA. Functional evaluation of complete
CR  - sciatic, peroneal, and posterior tibial nerve lesions in the rat.
CR  - Plast Reconstr Surg 1989;83:129–38.
CR  - Fu SY, Gordon T. Contributing factors to poor functional recovery
CR  - after delayed nerve repair: prolonged axotomy. J Neurosci
CR  - ;15:3876–85.
CR  - Kobayashi J, Mackinnon SE, Watanabe O, Ball DJ, Gu XM, Hunter
CR  - DA, Kuzon WM Jr. The effect of duration of muscle denervation on
CR  - functional recovery in the rat model. Muscle Nerve 1997;20:858–66.
CR  - Totosy de Zepetnek JE, Zung HV, Erdebil S, Gordon T.
CR  - Innervation ratio is an important determinant of force in normal and
CR  - reinnervated rat tibialis anterior muscles. J Neurophysiol 1992;67:
CR  - –403.
CR  - Viguie CA, Lu DX, Huang SK, Rengen H, Carlson BM.
CR  - Quantitative study of the effects of long-term denervation on the
CR  - extensor digitorum longus muscle of the rat. Anat Rec 1997;248:
CR  - –54.
CR  - Gordon T, Fu SY. Long-term response to nerve injury. Adv Neurol
CR  - ;72:185–99.
CR  - Sulaiman OA, Gordon T. Effects of short- and long-term Schwann
CR  - cell denervation on peripheral nerve regeneration, myelination, and
CR  - size. Glia 2000;32:234–46.
CR  - Hizay A, Demirel BM, Gokhan G, Sarikcioglu L, Demir N. Does
CR  - FK506 reduce the size of the watershed area after vascular injury of
CR  - the sciatic nerve? Rom J Morphol Embryol 2011;52:1077–80.
CR  - Sarikcioglu L, Demir N, Akar Y, Demirtop A. Effect of intrathecal
CR  - FK506 administration on intraorbital optic nerve crush: an ultrastructural
CR  - study. Can J Ophthalmol 2009;44:427–30.
CR  - Utuk A, Sarikcioglu L, Demirel BM, Demir N. The immunosuppressive
CR  - agent FK506 prevents subperineurial degeneration and
CR  - demyelination on ultrastructural and functional analysis. Curr
CR  - Neurovasc Res 2009;6:252–8.
CR  - Yildirim FB, Sarikcioglu L, Ozsoy U, Demir N, Demirtop A, Ucar
CR  - Y. Effect of FK506 administration after obturator nerve injury: a
CR  - functional and ultrastructural study. Acta Neurobiol Exp (Wars)
CR  - ; 68:477–83.
CR  - Ma J, Novikov LN, Wiberg M, Kellerth JO. Delayed loss of spinal
CR  - motoneurons after peripheral nerve injury in adult rats: a quantitative
CR  - morphological study. Exp Brain Res 2001;139:216–23.
CR  - Guntinas-Lichius O, Effenberger K, Angelov DN, Klein J, Streppel
CR  - M, Stennert E, Neiss WF. Delayed rat facial nerve repair leads to
CR  - accelerated and enhanced muscle reinnervation with reduced collateral
CR  - axonal sprouting during a definite denervation period using a
CR  - cross-anastomosis paradigm. Exp Neurol 2000;162:98–111.
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