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DOI: 10.1055/s-0041-1736467
Efeito dos imunossupressores tacrolimus e ciclosporina na regeneração de nervos periféricos: Revisão sistemática e metanálises
Article in several languages: português | English
Resumo
As lesões nervosas periféricas são uma causa importante de busca por atendimento médico. Elas ocorrem quando há a interrupção da continuidade das estruturas e do bloqueio da propagação dos impulsos nervosos, afetando a capacidade funcional dos indivíduos. Para avaliar os efeitos dos imunossupressores tacrolimus e ciclosporina na regeneração de nervos periféricos, foi realizada uma revisão sistemática da literatura. Foram incluídos artigos publicados até setembro de 2018, que se propunham avaliar os efeitos dos imunossupressores tacrolimus e ciclosporina na regeneração nervosa e neuroproteção, disponíveis nas bases de dados MEDLINE, EMBASE, Cochrane Library, Web of Science, Oxford Pain Relief Database e LILACS. A pesquisa analisou um total de 56 artigos, dos quais 22 foram para metanálise. A análise estatística sugere o efeito protetor do tacrolimus na regeneração do número de axônios mielinizados (intervalo de confiança [IC] 95%: 0,93–2,39; p < 0,01); todavia tal efeito não foi observado em relação à ciclosporina (IC95%: - 0,38–1,18; p = 0,08). Ela também sugere haver uma relação significativa entre o uso do tacrolimus e a espessura da mielina (IC95%: 2,00–5,71; p < 0,01). O uso de imunossupressores na regeneração de lesão nervosa periférica promove um aumento no número de axônios mielinizados de forma geral, independentemente da dose administrada. Além disso, garante uma maior espessura da mielina, um maior peso muscular e restabelecimento do índice da função do nervo ciático. Todavia, a heterogeneidade foi alta na maioria das análises realizadas.
Palavras-chave
regeneração nervosa - nervo periférico - imunossupressores - FK506 - tacrolimus - ciclosporinaPublication History
Received: 18 January 2021
Accepted: 12 April 2021
Article published online:
27 May 2022
© 2022. Sociedade Brasileira de Ortopedia e Traumatologia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)
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Referências
- 1 Sasso L. Análise comparativa da fotobioestimulação e da sinvastatina após lesão por esmagamento do nervo ciático em camundongos [TCC - graduação em Fisioterapia]. Araranguá: Universidade Federal de Santa Catarina; 2017
- 2 Barbosa RI, Marcolino AM, de Jesus Guirro RR, Mazzer N, Barbieri CH, de Cássia Registro Fonseca M. Comparative effects of wavelengths of low-power laser in regeneration of sciatic nerve in rats following crushing lesion. Lasers Med Sci 2010; 25 (03) 423-430
- 3 Oliveira FB, Pereira VM, da Trindade AP, Shimano AC, Gabriel RE, Borges AP. Action of therapeutic laser and ultrasound in peripheral nerve regeneration. Acta Ortop Bras 2012; 20 (02) 98-103
- 4 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 (02) 303-310
- 5 Luiz L. Avaliação da lesão nervosa periférica por meio da eletromiografia de superfície [dissertação]. Uberlândia - MG: Universidade Federal de Uberlândia; 2015
- 6 Wang CZ, Chen YJ, Wang YH. et al. Low-level laser irradiation improves functional recovery and nerve regeneration in sciatic nerve crush rat injury model. PLoS One 2014; 9 (08) e103348
- 7 Lundborg G, Rosén B. Hand function after nerve repair. In: Acta Physiologica. Vol 189. Acta Physiol (Oxf); 2007: 207-217
- 8 Yin Y, Xiao G, Zhang K. et al. Tacrolimus- and Nerve Growth Factor-Treated Allografts for Neural Tissue Regeneration. ACS Chem Neurosci 2019; 10 (03) 1411-1419
- 9 Tuma P, Ferreira MC, Nakamoto HA. et al. Influência da imunossupressão na regeneração nervosa com utilização de aloenxertos. Estudo experimental em ratos. Acta Ortop Bras 2008; 16 (01) 41-44
- 10 Udina E, Rodríguez FJ, Verdú E, Espejo M, Gold BG, Navarro X. FK506 enhances regeneration of axons across long peripheral nerve gaps repaired with collagen guides seeded with allogeneic Schwann cells. Glia 2004; 47 (02) 120-129
- 11 Grinsell D, Keating CP. Peripheral nerve reconstruction after injury: a review of clinical and experimental therapies. BioMed Res Int 2014; 2014: 698256
- 12 Taskinen HS, Röyttä M. Cyclosporin A affects axons and macrophages during Wallerian degeneration. J Neurotrauma 2000; 17 (05) 431-440
- 13 Meirer R, Babuccu O, Unsal M. et al. Effect of chronic cyclosporine administration on peripheral nerve regeneration: a dose-response study. Ann Plast Surg 2002; 49 (01) 96-103
- 14 Konofaos P, Terzis JK. FK506 and nerve regeneration: past, present, and future. J Reconstr Microsurg 2013; 29 (03) 141-148
- 15 Mohammadi R, Heydarian H, Amini K. Effect of local administration of cyclosporine A on peripheral nerve regeneration in a rat sciatic nerve transection model. Chin J Traumatol 2014; 17 (01) 12-18
- 16 Higgins JP, Green S. Eds. Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0. The Cochrane Collaboration. 2011 [updated March 2011]. Available from http://handbook.cochrane.org/
- 17 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 (07) 905-915
- 18 McGrath AM, Brohlin M, Wiberg R. et al. Long-Term Effects of Fibrin Conduit with Human Mesenchymal Stem Cells and Immunosuppression after Peripheral Nerve Repair in a Xenogenic Model. Cell Med 2018; 10: 2155179018760327
- 19 Jost SC, Doolabh VB, Mackinnon SE, Lee M, Hunter D. Acceleration of peripheral nerve regeneration following FK506 administration. Restor Neurol Neurosci 2000; 17 (01) 39-44
- 20 Ogden MA, Feng FY, Myckatyn TM. et al. Safe injection of cultured schwann cells into peripheral nerve allografts. Microsurgery 2000; 20 (07) 314-323
- 21 Sulaiman OAR, 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 (01) 127-137
- 22 Myckatyn TM, Ellis RA, Grand AG. et al. The effects of rapamycin in murine peripheral nerve isografts and allografts. Plast Reconstr Surg 2002; 109 (07) 2405-2417
- 23 Sobol JB, Lowe III JB, Yang RK, Sen SK, Hunter DA, Mackinnon SE. Effects of delaying FK506 administration on neuroregeneration in a rodent model. J Reconstr Microsurg 2003; 19 (02) 113-118
- 24 Brenner MJ, Fox IK, Kawamura DH. et al. Delayed nerve repair is associated with diminished neuroenhancement by FK506. Laryngoscope 2004; 114 (03) 570-576
- 25 Snyder AK, Fox IK, Nichols CM. et al. Neuroregenerative effects of preinjury FK-506 administration. Plast Reconstr Surg 2006; 118 (02) 360-367
- 26 Udina E, Ceballos D, Verdú E, Gold BG, Navarro X. Bimodal dose-dependence of FK506 on the rate of axonal regeneration in mouse peripheral nerve. Muscle Nerve 2002; 26 (03) 348-355
- 27 Song Y, Wang Z, Wang Z, Zhang H, Li X, Chen B. Use of FK506 and bone marrow mesenchymal stem cells for rat hind limb allografts. Neural Regen Res 2012; 7 (34) 2681-2688
- 28 Sun HH, Saheb-Al-Zamani M, Yan Y, Hunter DA, Mackinnon SE, Johnson PJ. Geldanamycin accelerated peripheral nerve regeneration in comparison to FK-506 in vivo. Neuroscience 2012; 223: 114-123
- 29 Grumbles RM, Casella GTB, Rudinsky MJ, Godfrey S, Wood PM, Thomas CK. The immunophilin ligand FK506, but not the P38 kinase inhibitor SB203580, improves function of adult rat muscle reinnervated from transplants of embryonic neurons. Neuroscience 2005; 130 (03) 619-630
- 30 Cottrell BL, Perez-Abadia G, Onifer SM. et al. Neuroregeneration in composite tissue allografts: effect of low-dose FK506 and mycophenolate mofetil immunotherapy. Plast Reconstr Surg 2006; 118 (03) 615-623 , discussion 624–625
- 31 Scharpf J, Strome M, Siemionow M. Immunomodulation with anti-alphabeta T-cell receptor monoclonal antibodies in combination with cyclosporine A improves regeneration in nerve allografts. Microsurgery 2006; 26 (08) 599-607
- 32 Kvist M, Sondell M, Kanje M, Dahlin LB. Regeneration in, and properties of, extracted peripheral nerve allografts and xenografts. J Plast Surg Hand Surg 2011; 45 (03) 122-128
- 33 Udina E, Gold BG, Navarro X. Comparison of continuous and discontinuous FK506 administration on autograft or allograft repair of sciatic nerve resection. Muscle Nerve 2004; 29 (06) 812-822
- 34 McGrath AM, Brohlin M, Kingham PJ, Novikov LN, Wiberg M, Novikova LN. Fibrin conduit supplemented with human mesenchymal stem cells and immunosuppressive treatment enhances regeneration after peripheral nerve injury. Neurosci Lett 2012; 516 (02) 171-176
- 35 Grand AG, Myckatyn TM, Mackinnon SE, Hunter DA. Axonal regeneration after cold preservation of nerve allografts and immunosuppression with tacrolimus in mice. J Neurosurg 2002; 96 (05) 924-932
- 36 Utuk A, Sarikcioglu L, Demirel BM, Demir N. The immunosuppressive agent FK506 prevents subperineurial degeneration and demyelination on ultrastructural and functional analysis. Curr Neurovasc Res 2009; 6 (04) 252-258
- 37 Shahraki M, Mohammadi R, Najafpour A. Influence of Tacrolimus (FK506) on Nerve Regeneration Using Allografts: A Rat Sciatic Nerve Model. J Oral Maxillofac Surg 2015; 73 (07) 1438.e1-1438.e9
- 38 Tulaci KG, Tuzuner A, Karadas Emir H. et al. The effect of tacrolimus on facial nerve injury: Histopathological findings in a rabbit model. Am J Otolaryngol 2016; 37 (05) 393-397
- 39 Azizi S, Mohammadi R, Amini K, Fallah R. Effects of topically administered FK506 on sciatic nerve regeneration and reinnervation after vein graft repair of short nerve gaps. Neurosurg Focus 2012; 32 (05) E5
- 40 Costa MP, Cunha AS, Silva CF. et al. A utilização do tubo de ácido poliglicólico e FK506 na regeneração de nervos periféricos. Acta Ortop Bras 2006; 14 (01) 25-29
- 41 Que J, Cao Q, Sui T. et al. Tacrolimus reduces scar formation and promotes sciatic nerve regeneration. Neural Regen Res 2012; 7 (32) 2500-2506
- 42 Rustemeyer J, van de Wal R, Keipert C, Dicke U. Administration of low-dose FK 506 accelerates histomorphometric regeneration and functional outcomes after allograft nerve repair in a rat model. J Craniomaxillofac Surg 2010; 38 (02) 134-140
- 43 Kim YT, Hei WH, Kim S. et al. Co-treatment effect of pulsed electromagnetic field (PEMF) with human dental pulp stromal cells and FK506 on the regeneration of crush injured rat sciatic nerve. Int J Neurosci 2015; 125 (10) 774-783