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EFFECT OF FK506 ADMINISTRATION IN ALPHA MOTOR NEURONS AFTER PRIMARY AND DELAYED REPAIR OF THE SCIATIC NERVE

Year 2016, Volume: 10 Issue: 1, 30 - 39, 30.04.2016

Abstract

Objectives: FK506 is an effective immunosuppressive drug for treating graft rejection in transplants patients. However, the neuroregenerative effect of FK506 has been well described in the literature. The aim of this study was to investigate the effects of 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 recovery level 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 and delayed repair groups.

References

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Year 2016, Volume: 10 Issue: 1, 30 - 39, 30.04.2016

Abstract

References

  • Aldskogius H, Kozlova EN. Central neuron-glial and glial-glial
  • interactions following axon injury. Prog Neurobiol 1998;55:1–26.
  • Bisby MA, Tetzlaff W. Changes in cytoskeletal protein synthesis following
  • axon injury and during axon regeneration. Mol Neurobiol
  • ;6:107–23.
  • de la Cruz RR, Pastor AM, Delgado-Garcia JM. Influence of the
  • postsynaptic target on the functional properties of neurons in the
  • adult mammalian central nervous system. Rev Neurosci 1996;7:115–
  • Lowrie MB, Vrbova G. Dependence of postnatal motoneurones on
  • their targets: review and hypothesis. Trends Neurosci 1992;15:80–4.
  • Hefti F. Pharmacology of neurotrophic factors. Annu Rev
  • Pharmacol Toxicol 1997;37:239–67.
  • Lindsay RM. Neurotrophins and receptors. Prog Brain Res
  • ;103:3–14.
  • Muller HW. Gene expression in nerve regeneration. Diabet Med
  • ;13:682.
  • Sendtner M. Neurotrophic factors for experimental treatment of
  • motoneuron disease. Prog Brain Res 1996;109:365–71.
  • Terenghi G. Peripheral nerve regeneration and neurotrophic factors.
  • J Anat 1999;194:1–14.
  • Snider WD, Elliott JL, Yan Q. Axotomy-induced neuronal death
  • during development. J Neurobiol 1992;23:1231–46.
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  • Ultrastructural study on avulsion effects of the cat cervical motoaxonal
  • pathways in the spinal cord. Clin Neurol Neurosurg 1993;95:
  • S39–47.
  • Martin LJ, Kaiser A, Price AC. Motor neuron degeneration after sciatic
  • nerve avulsion in adult rat evolves with oxidative stress and is
  • apoptosis. J Neurobiol 1999;40:185–201.
  • Novikov L, Novikova L, Kellerth JO. Brain-derived neurotrophic
  • factor promotes survival and blocks nitric oxide synthase expression
  • in adult rat spinal motoneurons after ventral root avulsion. Neurosci
  • Lett 1995;200:45–8.
  • Wu W. Expression of nitric-oxide synthase (NOS) in injured CNS
  • neurons as shown by NADPH diaphorase histochemistry. Exp
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  • neuropeptides and neurotrophic factor receptors following axotomy
  • in adult and ageing rats. Neuroscience 1998;84:141–50.
  • Mattsson P, Meijer B, Svensson M. Extensive neuronal cell death
  • following intracranial transection of the facial nerve in the adult rat.
  • Brain Res Bull 1999;49:333–41.
  • Tornqvist E, Aldskogius H. Motoneuron survival is not affected by
  • the proximo-distal level of axotomy but by the possibility of regenerating
  • axons to gain access to the distal nerve stump. J Neurosci Res
  • ;39:159–65.
  • Yu WH. Regulation of nitric oxide synthase expression in motoneurons
  • following nerve injury. Dev Neurosci 1997;19:247–54.
  • Arvidsson J, Aldskogius H. Effect of repeated hypoglossal nerve
  • lesions on the number of neurons in the hypoglossal nucleus of adult
  • rats. Exp Neurol 1982;75:520–4.
  • Crews LL, Wigston DJ. The dependence of motoneurons on their
  • target muscle during postnatal development of the mouse. J
  • Neurosci 1990;10:1643–53.
  • Johnson IP, Sears TA, Hunter AS. Retrograde response to axotomy
  • of motoneurons in the thoracic spinal cord of the aging cat.
  • Neurobiol Aging 1991;12:151–60.
  • Kuzis K, Coffin JD, Eckenstein FP. Time course and age dependence
  • of motor neuron death following facial nerve crush injury: role
  • of fibroblast growth factor. Exp Neurol 1999;157:77–87.
  • Anneser JM, Berthele A, Borasio GD, Castro-Lopes JM,
  • Zieglgansberger W, Tolle TR. Axotomy of the sciatic nerve differentially
  • affects expression of metabotropic glutamate receptor
  • mRNA in adult rat motoneurons. Brain Res 2000;868:215–21.
  • Vanden Noven S, Wallace N, Muccio D, Turtz A, Pinter MJ. Adult
  • spinal motoneurons remain viable despite prolonged absence of
  • functional synaptic contact with muscle. Exp Neurol 1993;123:147–
  • Kim HS, Park YI. Isolation and identification of a novel microorganism
  • producing the immunosuppressant tacrolimus. J Biosci
  • Bioeng 2008;105:418–21.
  • Abraham RT, Wiederrecht GJ. Immunopharmacology of
  • rapamycin. Annu Rev Immunol 1996;14:483–510.
  • Dumont FJ, Ok H, Lin S, Kastner CA, Cryan J, Martin MM,
  • Wiederrecht G, Staruch MJ. Mixed agonist/antagonist activity of an
  • FK-506-related immunosuppressant: biological and biochemical
  • characterization. J Pharmacol Exp Ther 1996;276:1078–88.
  • Brenner MJ, Fox IK, Kawamura DH, Yu VM, Lowe JB 3rd, Hunter
  • DA, Mackinnon SE. Delayed nerve repair is associated with diminished
  • neuroenhancement by FK506. Laryngoscope 2004;114:570–6.
  • Costantini LC, Chaturvedi P, Armistead DM, McCaffrey PG,
  • Deacon TW, Isacson O. A novel immunophilin ligand: distinct
  • branching effects on dopaminergic neurons in culture and neurotrophic actions after oral administration in an animal model of
  • Parkinson's disease. Neurobiol Dis 1998;5:97–106.
  • Arii T, Kamiya T, Arii K, Ueda M, Nito C, Katsura KI, Katayama
  • Y. Neuroprotective effect of immunosuppressant FK506 in transient
  • focal ischemia in rat: therapeutic time window for FK506 in transient
  • focal ischemia. Neurol Res 2001;23:755–60.
  • Ebisu T, Katsuta K, Fujikawa A, Aoki I, Umeda M, Naruse S,
  • Tanaka C. Early and delayed neuroprotective effects of FK506 on
  • experimental focal ischemia quantitatively assessed by diffusionweighted
  • MRI. Magn Reson Imaging 2001;19:153–60.
  • Sharkey J, Butcher SP. Immunophilins mediate the neuroprotective
  • effects of FK506 in focal cerebral ischaemia. Nature 1994;371:336–9.
  • Bavetta S, Hamlyn PJ, Burnstock G, Lieberman AR, Anderson PN.
  • The effects of FK506 on dorsal column axons following spinal cord
  • injury in adult rats: neuroprotection and local regeneration. Exp
  • Neurol 1999;158:382–93.
  • Madsen JR, MacDonald P, Irwin N, Goldberg DE, Yao GL, Meiri
  • KF, Rimm IJ, Stieg PE, Benowitz LI. Tacrolimus (FK506) increases
  • neuronal expression of GAP-43 and improves functional recovery
  • after spinal cord injury in rats. Exp Neurol 1998;154:673–83.
  • Gold BG, Yew JY, Zeleny-Pooley M. The immunosuppressant
  • FK506 increases GAP-43 mRNA levels in axotomized sensory neurons.
  • Neurosci Lett 1998;241:25–8.
  • Lyons WE, George EB, Dawson TM, Steiner JP, Snyder SH.
  • Immunosuppressant FK506 promotes neurite outgrowth in cultures
  • of PC12 cells and sensory ganglia. Proc Natl Acad Sci USA
  • ;91:3191–5.
  • Gold BG, Gordon HS, Wang MS. 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;267:33–6.
  • Gold BG, Katoh K, Storm-Dickerson T. The immunosuppressant
  • FK506 increases the rate of axonal regeneration in rat sciatic nerve.
  • J Neurosci 1995;15:7509–16.
  • Lee M, Doolabh VB, Mackinnon SE, Jost S. FK506 promotes functional
  • recovery in crushed rat sciatic nerve. Muscle Nerve
  • ;23:633–40.
  • Wang MS, Zeleny-Pooley M, Gold BG. 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:
  • –93.
  • Navarro X, Udina E, Ceballos D, Gold BG. Effects of FK506 on
  • nerve regeneration and reinnervation after graft or tube repair of
  • long nerve gaps. Muscle Nerve 2001;24:905–15.
  • Sarikcioglu L, Duygulu E, Aydin H, Gurer EI, Ozkan O, Tuzuner
  • S. Effects of intrathecal administration of FK506 after sciatic nerve
  • crush injury. J Reconstr Microsurg 2006;22:649–54.
  • Sobol JB, Lowe IJ, Yang RK, Sen SK, Hunter DA, Mackinnon SE.
  • Effects of delaying FK506 administration on neuroregeneration in a
  • rodent model. J Reconstr Microsurg 2003;19:113–8.
  • Chunasuwankul R, Ayrout C, Dereli Z, Gal A, Lanzetta M, Owen E.
  • Low dose discontinued FK506 treatment enhances peripheral nerve
  • regeneration. Int Surg 2002;87:274–8.
  • Jost SC, Doolabh VB, Mackinnon SE, Lee M, Hunter D.
  • Acceleration of peripheral nerve regeneration following FK506
  • administration. Restor Neurol Neurosci 2000;17:39–44.
  • Sulaiman OA, Midha R, Munro CA, Matsuyama T, Al-Majed A,
  • Gordon T. Chronic Schwann cell denervation and the presence of a
  • sensory nerve reduce motor axonal regeneration. Exp Neurol
  • ;176:342–54.
  • Sulaiman OA, Voda J, Gold BG, Gordon T. FK506 increases
  • peripheral nerve regeneration after chronic axotomy but not after
  • chronic schwann cell denervation. Exp Neurol 2002;175:127–37.
  • Pockett S, Gavin RM. Acceleration of peripheral nerve regeneration
  • after crush injury in rat. Neurosci Lett 1985;59:221–4.
  • Doolabh VB, Mackinnon SE. FK506 accelerates functional recovery
  • following nerve grafting in a rat model. Plast Reconstr Surg 1999;
  • :1928–36.
  • Fansa H, Keilhoff G, Altmann S, Plogmeier K, Wolf G, Schneider
  • W. The effect of the immunosuppressant FK 506 on peripheral
  • nerve regeneration following nerve grafting. J Hand Surg Br 1999;
  • :38–42.
  • Yang RK, Lowe JB, 3rd, Sobol JB, Sen SK, Hunter DA, Mackinnon
  • SE. Dose-dependent effects of FK506 on neuroregeneration in a rat
  • model. Plast Reconstr Surg 2003;112:1832–40.
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There are 244 citations in total.

Details

Primary Language English
Subjects Health Care Administration
Journal Section Original Articles
Authors

Umut Özsoy This is me

Fatoş Belgin Yıldırım This is me

Bahadır Murat Demirel This is me

Arzu Hızay This is me

Levent Sarıkcıoğlu

Necdet Demir This is me

Gamze Tanrıöver This is me

Bikem Süzen This is me

Nurettin Oğuz This is me

Publication Date April 30, 2016
Published in Issue Year 2016 Volume: 10 Issue: 1

Cite

APA Özsoy, U., Yıldırım, F. B., Demirel, B. M., Hızay, A., et al. (2016). EFFECT OF FK506 ADMINISTRATION IN ALPHA MOTOR NEURONS AFTER PRIMARY AND DELAYED REPAIR OF THE SCIATIC NERVE. Anatomy, 10(1), 30-39.
AMA Özsoy U, Yıldırım FB, Demirel BM, Hızay A, Sarıkcıoğlu L, Demir N, Tanrıöver G, Süzen B, Oğuz N. EFFECT OF FK506 ADMINISTRATION IN ALPHA MOTOR NEURONS AFTER PRIMARY AND DELAYED REPAIR OF THE SCIATIC NERVE. Anatomy. June 2016;10(1):30-39.
Chicago Özsoy, Umut, Fatoş Belgin Yıldırım, Bahadır Murat Demirel, Arzu Hızay, Levent Sarıkcıoğlu, Necdet Demir, Gamze Tanrıöver, Bikem Süzen, and Nurettin Oğuz. “EFFECT OF FK506 ADMINISTRATION IN ALPHA MOTOR NEURONS AFTER PRIMARY AND DELAYED REPAIR OF THE SCIATIC NERVE”. Anatomy 10, no. 1 (June 2016): 30-39.
EndNote Özsoy U, Yıldırım FB, Demirel BM, Hızay A, Sarıkcıoğlu L, Demir N, Tanrıöver G, Süzen B, Oğuz N (June 1, 2016) EFFECT OF FK506 ADMINISTRATION IN ALPHA MOTOR NEURONS AFTER PRIMARY AND DELAYED REPAIR OF THE SCIATIC NERVE. Anatomy 10 1 30–39.
IEEE U. Özsoy, F. B. Yıldırım, B. M. Demirel, A. Hızay, L. Sarıkcıoğlu, N. Demir, G. Tanrıöver, B. Süzen, and N. Oğuz, “EFFECT OF FK506 ADMINISTRATION IN ALPHA MOTOR NEURONS AFTER PRIMARY AND DELAYED REPAIR OF THE SCIATIC NERVE”, Anatomy, vol. 10, no. 1, pp. 30–39, 2016.
ISNAD Özsoy, Umut et al. “EFFECT OF FK506 ADMINISTRATION IN ALPHA MOTOR NEURONS AFTER PRIMARY AND DELAYED REPAIR OF THE SCIATIC NERVE”. Anatomy 10/1 (June 2016), 30-39.
JAMA Özsoy U, Yıldırım FB, Demirel BM, Hızay A, Sarıkcıoğlu L, Demir N, Tanrıöver G, Süzen B, Oğuz N. EFFECT OF FK506 ADMINISTRATION IN ALPHA MOTOR NEURONS AFTER PRIMARY AND DELAYED REPAIR OF THE SCIATIC NERVE. Anatomy. 2016;10:30–39.
MLA Özsoy, Umut et al. “EFFECT OF FK506 ADMINISTRATION IN ALPHA MOTOR NEURONS AFTER PRIMARY AND DELAYED REPAIR OF THE SCIATIC NERVE”. Anatomy, vol. 10, no. 1, 2016, pp. 30-39.
Vancouver Özsoy U, Yıldırım FB, Demirel BM, Hızay A, Sarıkcıoğlu L, Demir N, Tanrıöver G, Süzen B, Oğuz N. EFFECT OF FK506 ADMINISTRATION IN ALPHA MOTOR NEURONS AFTER PRIMARY AND DELAYED REPAIR OF THE SCIATIC NERVE. Anatomy. 2016;10(1):30-9.

Anatomy is the official journal of Turkish Society of Anatomy and Clinical Anatomy (TSACA).