Skip to main content Skip to main navigation menu Skip to site footer

Peripheral nerve injury and its regeneration processes: a biomolecular point of view

  • Tito - Sumarwoto ,
  • Cakradenta Yudha Poetera ,
  • Dimitri Abimanyu ,

Abstract

Peripheral nerve regeneration occurs spontaneously after injury due to the permissive environment and activation of the intrinsic growth capacity of neurons. Injuries can be divided into three categories: neurapraxia, axonotmesis and neurotmesis. Wallerian degeneration occurs due to axonotmesis and neurotmesis, affecting the axon distal to the site of damage. After this phase is complete, the damaged neurons try to rebuild the damaged fibers with axonal budding. Axonal growth can occur efficiently, which is influenced by signaling molecules and the integrity of the connective tissue tunnel. It can allow axons to grow back in the right direction and innervate the innervation of the target tissue.

References

  1. Zuo KJ, Gordon T, Chan KM, Borschel GH. Electrical stimulation to enhance peripheral nerve regeneration: Update in molecular investigations and clinical translation. Exp Neurol. 2020;332:113397. Available from: http://dx.doi.org/10.1016/j.expneurol.2020.113397
  2. Alarhayem AQ, Cohn SM, Cantu-Nunez O, Eastridge BJ, Rasmussen TE. Impact of time to repair on outcomes in patients with lower extremity arterial injuries. J Vasc Surg. 2019;69(5):1519–23. Available from: http://dx.doi.org/10.1016/j.jvs.2018.07.075
  3. Tian L, Prabhakaran MP, Ramakrishna S. Strategies for regeneration of components of nervous system: scaffolds, cells and biomolecules. Regen Biomater. 2015/01/13. 2015;2(1):31–45. Available from: https://pubmed.ncbi.nlm.nih.gov/26813399
  4. Chhabra A, Ahlawat S, Belzberg A, Andreseik G. Peripheral nerve injury grading simplified on MR neurography: As referenced to Seddon and Sunderland classifications. Indian J Radiol Imaging. 2014;24(3):217–24. Available from: https://pubmed.ncbi.nlm.nih.gov/25114384
  5. Carvalho CR, Reis RL, Oliveira JM. Fundamentals and Current Strategies for Peripheral Nerve Repair and Regeneration [Internet]. Advances in Experimental Medicine and Biology. Springer Singapore; 2020. p. 173–201. Available from: http://dx.doi.org/10.1007/978-981-15-3258-0_12
  6. Yousefi F, Lavi Arab F, Nikkhah K, Amiri H, Mahmoudi M. Novel approaches using mesenchymal stem cells for curing peripheral nerve injuries. Life Sci. 2019;221:99–108. Available from: http://dx.doi.org/10.1016/j.lfs.2019.01.052
  7. Li R, Li D-H, Zhang H-Y, Wang J, Li X-K, Xiao J. Growth factors-based therapeutic strategies and their underlying signaling mechanisms for peripheral nerve regeneration. Acta Pharmacol Sin. 2020/03/02. 2020;41(10):1289–300. Available from: https://pubmed.ncbi.nlm.nih.gov/32123299
  8. Vijayavenkataraman S. Nerve guide conduits for peripheral nerve injury repair: A review on design, materials and fabrication methods. Acta Biomater. 2020;106:54–69. Available from: http://dx.doi.org/10.1016/j.actbio.2020.02.003
  9. Seddon HJ. Three Types of Nerve Injury. Brain. 1943;66(4):237–88. Available from: http://dx.doi.org/10.1093/brain/66.4.237
  10. Panzer K V, Burrell JC, Helm KVT, Purvis EM, Zhang Q, Le AD, et al. Tissue Engineered Bands of Büngner for Accelerated Motor and Sensory Axonal Outgrowth. Front Bioeng Biotechnol. 2020;8:580654. Available from: https://pubmed.ncbi.nlm.nih.gov/33330416
  11. Grinsell D, Keating CP. Peripheral nerve reconstruction after injury: a review of clinical and experimental therapies. Biomed Res Int. 2014/09/03. 2014;2014:698256. Available from: https://pubmed.ncbi.nlm.nih.gov/25276813
  12. Sunderland S. A Classification of Peripheral Nerve Injuries Producing Loss of Function. Brain. 1951;74(4):491–516. Available from: http://dx.doi.org/10.1093/brain/74.4.491
  13. Modrak M, Talukder MAH, Gurgenashvili K, Noble M, Elfar JC. Peripheral nerve injury and myelination: Potential therapeutic strategies. J Neurosci Res. 2019/10/13. 2020;98(5):780–95. Available from: https://pubmed.ncbi.nlm.nih.gov/31608497
  14. Millesi F, Weiss T, Mann A, Haertinger M, Semmler L, Supper P, et al. Defining the regenerative effects of native spider silk fibers on primary Schwann cells, sensory neurons, and nerve-associated fibroblasts. FASEB J. 2020/11/19. 2021;35(2):e21196–e21196. Available from: https://pubmed.ncbi.nlm.nih.gov/33210360
  15. Mackinnon S, Dellon A. Diagnosis of nerve injury. In: Surgery of the peripheral nerve. Thieme Medical Publishers; 1988. p. 74–80.
  16. Harianawala H, Kheur M, Kheur S, Sethi T, Bal A, Burhanpurwala M, et al. Biocompatibility of zirconia. J Adv Med Dent Sci Res. 2016;4(3):35.
  17. Caillaud M, Richard L, Vallat J-M, Desmoulière A, Billet F. Peripheral nerve regeneration and intraneural revascularization. Neural Regen Res. 2019;14(1):24–33. Available from: https://pubmed.ncbi.nlm.nih.gov/30531065
  18. Khan H, Perera N. Peripheral nerve injury: an update. Orthop Trauma. 2020;34(3):168–73. Available from: http://dx.doi.org/10.1016/j.mporth.2020.03.011
  19. Gordon T. Peripheral Nerve Regeneration and Muscle Reinnervation. Int J Mol Sci. 2020;21(22):8652. Available from: https://pubmed.ncbi.nlm.nih.gov/33212795
  20. Loreto A, Hill CS, Hewitt VL, Orsomando G, Angeletti C, Gilley J, et al. Mitochondrial impairment activates the Wallerian pathway through depletion of NMNAT2 leading to SARM1-dependent axon degeneration. Neurobiol Dis. 2019/11/15. 2020;134:104678. Available from: https://pubmed.ncbi.nlm.nih.gov/31740269
  21. Cheong H, Kim J, Kim BJ, Kim E, Park HY, Choi B-H, et al. Multi-dimensional bioinspired tactics using an engineered mussel protein glue-based nanofiber conduit for accelerated functional nerve regeneration. Acta Biomater. 2019;90:87–99. Available from: http://dx.doi.org/10.1016/j.actbio.2019.04.018
  22. Levi AD, Ross AL, Cuartas E, Qadir R, Temple HT. The Surgical Management of Symptomatic Peripheral Nerve Sheath Tumors. Neurosurgery. 2010;66(4):833–40. Available from: http://dx.doi.org/10.1227/01.neu.0000367636.91555.70
  23. Lu Y, Li R, Zhu J, Wu Y, Li D, Dong L, et al. Fibroblast growth factor 21 facilitates peripheral nerve regeneration through suppressing oxidative damage and autophagic cell death. J Cell Mol Med. 2018/11/18. 2019;23(1):497–511. Available from: https://pubmed.ncbi.nlm.nih.gov/30450828
  24. Yao C, Yu B. Role of Long Noncoding RNAs and Circular RNAs in Nerve Regeneration. Front Mol Neurosci. 2019;12:165. Available from: https://pubmed.ncbi.nlm.nih.gov/31316349
  25. Colazo JM, Evans BC, Farinas AF, Al-Kassis S, Duvall CL, Thayer WP. Applied Bioengineering in Tissue Reconstruction, Replacement, and Regeneration. Tissue Eng Part B Rev. 2019;25(4):259–90. Available from: https://pubmed.ncbi.nlm.nih.gov/30896342
  26. Sahar MSU, Barton M, Tansley GD. Bridging larger gaps in peripheral nerves using neural prosthetics and physical therapeutic agents. Neural Regen Res. 2019;14(7):1109–15. Available from: https://pubmed.ncbi.nlm.nih.gov/30804232
  27. Barton MJ, John JS, Clarke M, Wright A, Ekberg J. The Glia Response after Peripheral Nerve Injury: A Comparison between Schwann Cells and Olfactory Ensheathing Cells and Their Uses for Neural Regenerative Therapies. Int J Mol Sci. 2017;18(2):287. Available from: https://pubmed.ncbi.nlm.nih.gov/28146061
  28. Bastien D, Lacroix S. Cytokine pathways regulating glial and leukocyte function after spinal cord and peripheral nerve injury. Exp Neurol. 2014;258:62–77. Available from: http://dx.doi.org/10.1016/j.expneurol.2014.04.006
  29. Chen G, Luo X, Wang W, Wang Y, Zhu F, Wang W. Interleukin-1? Promotes Schwann Cells De-Differentiation in Wallerian Degeneration via the c-JUN/AP-1 Pathway. Front Cell Neurosci. 2019;13:304. Available from: https://pubmed.ncbi.nlm.nih.gov/31338026
  30. Zhang R, Zhang Y, Yi S. Identification of critical growth factors for peripheral nerve regeneration. RSC Adv. 2019;9(19):10760–5. Available from: http://dx.doi.org/10.1039/c9ra01710k
  31. Bhandari PS. Management of peripheral nerve injury. J Clin Orthop trauma. 2019/08/13. 2019;10(5):862–6. Available from: https://pubmed.ncbi.nlm.nih.gov/31528058
  32. Zhang BGX, Myers DE, Wallace GG, Brandt M, Choong PFM. Bioactive coatings for orthopaedic implants-recent trends in development of implant coatings. Int J Mol Sci. 2014;15(7):11878–921. Available from: https://pubmed.ncbi.nlm.nih.gov/25000263
  33. Liu Q, Wang X, Yi S. Pathophysiological Changes of Physical Barriers of Peripheral Nerves After Injury. Front Neurosci. 2018;12:597. Available from: https://pubmed.ncbi.nlm.nih.gov/30210280
  34. Wang X, Miao Y, Ni J, Wang Y, Qian T, Yu J, et al. Peripheral Nerve Injury Induces Dynamic Changes of Tight Junction Components. Front Physiol. 2018;9:1519. Available from: https://pubmed.ncbi.nlm.nih.gov/30425652
  35. Anand S, Desai V, Alsmadi N, Kanneganti A, Nguyen DH-T, Tran M, et al. Asymmetric Sensory-Motor Regeneration of Transected Peripheral Nerves Using Molecular Guidance Cues. Sci Rep. 2017;7(1):14323. Available from: https://pubmed.ncbi.nlm.nih.gov/29085079
  36. Stonner MM, Mackinnon SE, Kaskutas V. Predictors of functional outcome after peripheral nerve injury and compression. J Hand Ther. 2021;34(3):369–75. Available from: http://dx.doi.org/10.1016/j.jht.2020.03.008
  37. Masgutov R, Masgutova G, Mullakhmetova A, Zhuravleva M, Shulman A, Rogozhin A, et al. Adipose-Derived Mesenchymal Stem Cells Applied in Fibrin Glue Stimulate Peripheral Nerve Regeneration. Front Med. 2019;6:68. Available from: https://pubmed.ncbi.nlm.nih.gov/31024916
  38. Hara T, Tatebe M, Kurahashi T, Hirata H. Iatrogenic peripheral nerve injuries – Common causes and treatment: A retrospective single-center cohort study. J Orthop Sci. 2020; Available from: http://dx.doi.org/10.1016/j.jos.2020.09.009
  39. Rigoni M, Negro S. Signals Orchestrating Peripheral Nerve Repair. Cells. 2020;9(8):1768. Available from: https://pubmed.ncbi.nlm.nih.gov/32722089
  40. Nocera G, Jacob C. Mechanisms of Schwann cell plasticity involved in peripheral nerve repair after injury. Cell Mol Life Sci. 2020/04/10. 2020;77(20):3977–89. Available from: https://pubmed.ncbi.nlm.nih.gov/32277262
  41. Jones S, Eisenberg HM, Jia X. Advances and Future Applications of Augmented Peripheral Nerve Regeneration. Int J Mol Sci. 2016;17(9):1494. Available from: https://pubmed.ncbi.nlm.nih.gov/27618010
  42. Dubový P, Jan?álek R, Kubek T. Role of inflammation and cytokines in peripheral nerve regeneration. Int Rev Neurobiol. 2013;108:173–206. Available from: http://europepmc.org/abstract/MED/24083435
  43. Regas I, Loisel F, Haight H, Menu G, Obert L, Pluvy I. Functionalized nerve conduits for peripheral nerve regeneration: A literature review. Hand Surg Rehabil. 2020;39(5):343–51. Available from: http://dx.doi.org/10.1016/j.hansur.2020.05.007
  44. Knott EP, Assi M, Pearse DD. Cyclic AMP signaling: a molecular determinant of peripheral nerve regeneration. Biomed Res Int. 2014/08/07. 2014;2014:651625. Available from: https://pubmed.ncbi.nlm.nih.gov/25177696
  45. Zarrintaj P, Zangene E, Manouchehri S, Amirabad LM, Baheiraei N, Hadjighasem MR, et al. Conductive biomaterials as nerve conduits: Recent advances and future challenges. Appl Mater Today. 2020;20:100784. Available from: http://dx.doi.org/10.1016/j.apmt.2020.100784

How to Cite

Sumarwoto, T. .-., Poetera, C. Y., & Abimanyu, D. (2021). Peripheral nerve injury and its regeneration processes: a biomolecular point of view. Bali Medical Journal, 10(2), 927–934. https://doi.org/10.15562/bmj.v10i2.2343

HTML
0

Total
24

Share

Search Panel

Tito - Sumarwoto
Google Scholar
Pubmed
BMJ Journal


Cakradenta Yudha Poetera
Google Scholar
Pubmed
BMJ Journal


Dimitri Abimanyu
Google Scholar
Pubmed
BMJ Journal