Peripheral Nerve Injuries and Regeneration

Year 2022, , 211 - 219, 30.08.2022

İşınsu Alkan , Esra Bekar , Zuhal Altunkaynak

https://doi.org/10.46332/aemj.975395

Abstract

Peripheral nerves are a system consisting of various nerve fibers named according to the functions they stimulate in the target organ that provides motor and sensory stimulation between the central nervous system and peripheral organs. Peripheral nerves, which are quite open to trauma, are injured for different reasons. Damage to the peripheral nerves negatively affects the motor and sensory stimulation of the person. After peripheral injuries, degenerative processes are initiated due to damage to the peripheral nerve. In injuries that interrupt the axonal continuity, the distal parts of the axon degenerate because the metabolic events required for the continuity of the nerve function cannot occur in the axon. Schwann cell dedifferentiation, proliferation and remyelination play an important role in peripheral nerve regeneration. The regenerative process is a process where many factors work together. In this review, the regeneration process after peripheral nerve injuries, neurotrophic factors affecting regeneration and the mechanisms of action of different methods used in the treatment process are discussed.

Keywords

neurotrophic factor, peripheral nerve degeneration, peripheral nerve regeneration, schwann cell

Periferik Sinir Yaralanmaları ve Rejenerasyonu

Abstract

Periferik sinirler merkezi sinir sistemi ve periferal organlar arasındaki motor ve duyu uyarımını sağlayan hedef organda uyardıkları fonksiyonlara göre isimledirilen çeşitli sinir liflerinden oluşan sistemdir. Travmalara oldukça açık bulunan periferik sinirlerde farklı sebepler ile yaralanmalar gözlemlenir. Bu şekilde periferik sinirlerde oluşabilecek hasar kişinin motor ve duyu uyarımını olumsuz etkilemektedir. Periferal yaralanmaların ardından perifrerik sinirde hasara bağlı olarak dejeneratif süreçler başlatılır. Aksonal devamlılığı kesintiye uğratacak derecedeki yaralanmalarda aksonda sinir fonksiyonunun devamlılığı için gereken metabolik olaylar gerçekleşemediği için distal kısımlar dejenerasyona uğrar. Periferik sinir rejenerasyonunda Schwann hücre dediferansiyasyonu, proliferasyonu ve remiyelinizasyon önemli rol oynar. Rejeneratif süreç ise oldukça fazla faktörün bir arada çalıştığı bir süreçtir. Bu derlemede, periferik sinirde meydana gelen yaralanmaların ardından gerçekleşen rejenerasyon süreci, ayrıca rejenerasyona etki eden nörotrofik faktörler ve tedavi sürecinde kullanılan farklı metotların etki mekanizmalarına değinilmiştir.

Keywords

nörotrofik faktör, periferik sinir dejenerasyonu, periferik sinir rejenerasyonu, schwann hücresi

References

• 1. Önger ME, Altun G, Aydın I, ve ark. Periferik sinir için stereolojik inceleme yöntemi. Turkiye Klinikleri J Neurol-Special Topics. 2014;7(2):56-60.
• 2. Kayhan Kustepe E, Zuhal Altunkaynak B, Alkan I, Kivrak EG, Yildiran A, Geuna S. Potential Effects of Stem Cells Derived from the Peripheral Nerve and Adipose Tissue after the Nerve Crush Injury in Control and Obese Rats. J Invest Surg. 2022;35(5): 1021-1033.
• 3. Atalay FÖ, Üstün H. Periferik sinir sisteminde nöronal dejenerasyon, rejenerasyon ve nörodejeneratif hastalıklarda yeni tedavi modaliteleri. Fiziksel Tıp. 2004;7(3):157-162.
• 4. Garbay B, Heape AM, Sargueil F, et al. Myelin synthesis in peripheral nervous system. Prog Neurobiol. 2000;61(3):267-304.
• 5. Kaplan AA, Yurt KK, Deniz ÖG, ve ark. Peripheral nerve and diclofenac sodium: molecular and clinical approaches. J Chem Neuroanat. 2018;87:2-11.
• 6. Maggi SP, Lowe JB, Mackinnon SE. Pathophysiology of nerve injury. Clin Plast Surg. 2003;30(2):109-126.
• 7. Özmen S. Uç yan sinir anastomozunda alıcı sinir distal ucunda epinörium rezeksiyonunun rejenerasyona etkisi. Uzmanlık Tezi. Ankara:Gazi Üniversitesi Tıp Fakültesi;2002.
• 8. Thomas PK, Berthold CH, Ochoa J. Microscopic anatomy of the peripheral nervous system In: Dyck P. Peripheral Neuropathy. 3rd ed. Philadelphia: Saunders;1993:28-80.
• 9. Catala M, Kubis N. Gross anatomy and development of the peripheral nervous system. Handb Clin Neurol. 2013;115:29-41.
• 10. Lundborg, G. Nerve injury and repair: Regeneration, reconstruction and cortical remodelling. 2nd. Philadelphia: Churchill Livingstone; 2004:114-155.
• 11. Burnett MG, Zager EL. Pathophysiology of peripheral nerve injury: a brief review. Neurosurg Focus. 2004;16(5):1-7.
• 12. Hirakawa H, Okajima S, Nagaoka T, et al. Loss and recovery of the blood-nerve barrier in the rat sciatic nerve after crush injury are associated with expression of intercellular junctional proteins. Exp Cell Res. 2003;284(2):196-210.
• 13. Sütçü M. Periferik sinir kesisinde farklı onarım zamanlarında melatoninin sinir iyileşmesine olan etkisinin incelenmesi. Uzmanlık tezi. Konya:Selçuk Üniversitesi Meram Tıp Fakültesi, Plastik Rekonstrüktif Ve Estetik Cerrahi Anabilim Dalı;2010.
• 14. Demiryürek Ş, Demiryürek AT, Babül A. Periferik sinir hasarı ve dejenerasyonu. FABAD J Pham Sci. 2002;27:43-53.
• 15. Selzer ME, Regeneration of peripheral nevre In: Sumner AJ. The physiology of peripheral nerve disease.Philadelphia: W.B Saunders Company; 1980:358-431.
• 16. Letourneau, P.C. Immunocytochemical evidence for colocalization in neurite growth cones, of actin and myosin and their relationship to cell-substratum adhesions. Dev Biol. 1981;85(1):113.
• 17. Son YJ, Thompson WJ. Schwann cell processes guide regeneration of peripheral axons. Neuron. 1995;14(1):125-132.
• 18. Geuna S, Raimondo S, Ronchi G, et al., Chapter 3:Histology of the peripheral nerve and changes occurring during nerve regeneration. Int Rev Neurobiol. 2009;87:27-46.
• 19. Spencer PS. Morphology of the injured peripheral nerve. In: Daniel RK, Terzis JK. Reconstructive microsurgery. Boston: Little Brown and Company;1977:342:349.
• 20. Cattin AL, Lloyd AC. The multicellular complexity of peripheral nerve regeneration. Curr Opin Neurobiol. 2016;39:38-46.
• 21. Weiss P. The technology of nerve regeneration; a review. Sutureless tubulation and related methods of nerve repair. Neurosurg. 1944;1(6):400.
• 22. Krystosek A, Seeds NW. Plasminogen activatör release at the neural growth cone. Science. 1982;213(4515):1532.
• 23. Waller A. Experiments on the section of the glossopharyngeal and hypoglossal nerves of the frog, and observations of the alterations produced thereby in the structure of their primitive fibres. The Royal Society Philos. Trans. R. Soc. 1850;140:423-429.
• 24. Terenghi G. Peripheral nerve regeneration and neurotrophic factors. J Anat. 1999;194(1):1-14.
• 25. Dai J, Niyazi M, Xie J. Tissue engineering scaffold slowly releasing neurotrophic factors to bridge long peripheral nerve defect. J Biomater Tissue Eng. 2022;12(2):329-334.
• 26. Kaptanoğlu E. Omurilik rejenerasyonu ve kök hücre uygulamaları. Türk Fiz. Tıp Rehab. Derg. 2008;54(2):38-45.
• 27. Duru S, Kuzeyli K, Ceylanı S, et al. Effect of nevre growth factor on sciatic nerve regeneration following experimental repair. Turkiye Klinikleri J Med Res. 1997;15(1):1-5.
• 28. Lee AC, Yu VM, Lowe YB, et al. Controlled release of nerve growth factor enhances sciatic nerve regeneration. Exp. Neurol. 2003;184(1):295-303.
• 29. Midha R, Munro CA., Dalton PD, et al. Growth factor enhancement of peripheral nerve regeneration through a novel synthetic hydrogel tube. J Neurosurg. 2003;99(3):555-565.
• 30. Li R, Li D, Wu C, et al. Nerve growth factor activates autophagy in Schwann cells to enhance myelin debris clearance and to expedite nerve regeneration. Theranostics. 2020;10(4):1649-1677.
• 31. Gordon T. The role of neurotrophic factors in nevre regeneration. Neurosurg Focus. 2009;26(2):3.
• 32. McGregor CE, English AW. The Role of BDNF in peripheral nerve regeneration: activity-dependent treatments and Val66Met. Front Cell Neurosci. 2018;12:522.
• 33. Lin G, Zhang H, Sun F, et al. Brain-derived neurotrophic factor promotes nerve regeneration by activating the JAK/STAT pathway in Schwann cells. Transl Androl Urol. 2016;5(2):167-175.
• 34. Vögelin E, Baker JM, Gates J, et al. Effects of local continuous release of brain derived neurotrophic factor (BDNF) on peripheral nerve regeneration in a rat model. Exp Neurol. 2006;199(2):348-353.
• 35. Jiao Y, Palmgren B, Novozhilova E, et al. BDNF increases survival and neuronal differentiation of human neural precursor cells cotransplanted with a nanofiber gel to the auditory nerve in a rat model of neuronal damage. Biomed Res Int. 2014;2014:356415.
• 36. Schmitt JP, Seidman CE. Monogenic Causes of congenital heart disease. In: Kenneth RC ed. Molecular basis of cardiovascular disease. 2nd ed. Philadelphia;Elsevier 2004;261-271.
• 37. Dubový P, Raška O, Klusáková I, et al. Ciliary neurotrophic factor promotes motor reinnervation of the musculocutaneous nerve in an experimental model of end-to-side neurorrhaphy. BMC Neurosci. 2011;12(1):58.
• 38. Makwana M, Raivich G. Molecular mechanisms in successful peripheral regeneration. FEBS Journal. 2005;272(11):2628-2638.
• 39. Newman JP. Ciliary neurotrophic factors enhances periferal nerve regeneration. Otolaryngol Head Neck Surg. 1996;122(4):399-403.
• 40. Ogai K, Kuwana A, Hisano S, et al. Upregulation of Leukemia Inhibitory Factor (LIF) during the early stage of optic nerve regeneration in Zebrafish. PLoSONE. 2014;9(8):e106010.
• 41. Hart MA, Wiberg M, Terenghi G. Exogenous leukaemia inhibitory factor enhances nerve regeneration after late secondary repair using a bioartificial nerve conduit Br J Plast Surg. 2003;56(5):444-450.
• 42. Kubiczkova L, Sedlarikova L, Hajek R. et al. TGF-β –an excellent servant but a bad master. J Transl Med. 2012;10:183.
• 43. Eggers R, de Winter F, Tannemaat MR, et al. GDNF Gene therapy to repair the ınjured peripheral nerve. Front Bioeng Biotechnol. 2020;8:583184.
• 44. Shen Y, Mani S, Donovan SL, et al. Growth-Associated Protein-43 Is Required for Commissural Axon Guidance in the Developing Vertebrate Nervous System. J. Neurosci. Res. 2002;22(1):239-247.
• 45. Faweett JW, Keynes RJ. Peripheral nerve regeneration. Annu Rev Neurosci. 1990;13:43-60.
• 46. Davis GE, Manthope M, Williams LR, et al. Characterization of a laminin- containing neurite- promoting factor and a neuronotrophic factor from peripheral nerve related sources. Ann NY Acad Sci. 1986;486:194-205.
• 47. Chen ZL, Yu W, Strickland S. Peripheral nerve regeneration; a review. Annual Reviews Inc. 2007;30:209-233.
• 48. Widerberg A, Kanje M, Dahlin LB. Tourniquet compression: a non-invasive method to enhance nerve regeneration in nerve grafts. Neuroreport. 2002;13(4):371-375.
• 49. Ogata T, Iijima S, Hoshikawa S, et al. Opposing extracellular signal-regulated kinase and Akt pathways control Schwann cell myelination. J Neurosci. 2004;24(30):6724-6778.
• 50. Kim HA, Pomeroy SL, Whoriskey W, et al. A developmentally regulated switch directs regenerative growth of Schwann cells through cyclin D1. Neuron. 2000;26(2):405-478.
• 51. Masaki T, Matsumura K, Saito F, et al. Expression of dystroglycan and laminin-2 in peripheral nerve under axonal degeneration and regeneration. Acta Neuropathol. (Berlin) 2000;99(3):289-278.
• 52. Bracken MB, Shepard M, Holford TR, et al. Methylprednisolone or tirilazad mesilate administration after acute spinal cord injury: 1-year follow up. Results of the third National Acute Spinal Cord Injury Randomized controlled trial. J Neurosurg. 1998;89(5):699-706.
• 53. Akassoglou K, Yu WM, Akpinar P, et al. Fibrin inhibits peripheral nerve remyelination by regulating Schwann cell differentiation. Neuron. 2002;33(6):861-878.
• 54. Melcangi RC, Cavarretta IT, Ballabio M, et al. Peripheral nerves: a target for the action of neuroactive steroids. Brain Res. Rev. 2005;48(2):328-338.
• 55. Li X, Gonias SL, Campana WM. Schwann cells express erythropoietin receptor and represent a major target for Epo in peripheral nerve injury. Glia. 2005;51(4):254-278.