The rat's sciatic nerve functional index dynamics after its transection and recovery by means of epineural neurorrhaphy

Authors

DOI:

https://doi.org/10.25305/unj.310430

Keywords:

peripheral nerve injury, sciatic nerve transection, neurorrhaphy, sciatic nerve functional index, temporal dynamics of the indicator

Abstract

Introduction. Peripheral nerve injury (PNI) is a common wartime pathology, the presence of which significantly complicates the course and treatment of combat injuries to the limbs. The development of new methods of treatment of PNI is impossible without validating existing models of PNI and clarifying the dynamics of the recovery process in this type of injury over long periods of observation. In this paper, the dynamics of the sciatic functional index (SFI) after transection and immediate suturing of the sciatic nerve of an adult rat during 24 weeks of observation was analyzed in detail.

Objective: to analyze the dynamics of SFI after transection, as well as after transection and immediate suturing of the sciatic nerve of an adult rat for 24 weeks and compare the obtained results with the data of other authors under similar experimental conditions.

Materials and Methods. The study was performed on 76 white adult outbred male rats, adhering to bioethical norms. In animals of the Sham group (n=24) an access to the sciatic nerve was performed, in animals of the Sect group (n=29) — the sciatic nerve was transected, and Raph group (n=23) — transection and immediate epineural suturing of the sciatic nerve was performed. A certain number of animals were removed from each group 4, 8, and 12 weeks after surgery for electrophysiological and morphological studies, and for the rest of the animals, the experiment was completed 24 weeks after the start of observation. SFI was determined before animals were removed, for all animals in each group at 4, 8, 12, 16, 20 and 24 weeks according to the Bain-Mackinnon-Hunter formula. Processing of digital data was carried out by various means of mathematical statistics.

Results. In animals of the Sham group, which were observed throughout the entire 24 weeks of the experiment (n=7), the average value of SFI one month after the injury simulation was -8.9 points and did not change significantly until the end of the experiment. In animals of the Sect group, which were observed throughout the entire 24 weeks of the experiment (n=8), one month after the injury, the mean SFI value was –84.7 points, significantly increasing to –67.0 points at the end of the 16th week, and subsequently significantly decreasing to –96.5 points. In animals of the Raph group, which were observed throughout the entire 24 weeks of the experiment (n=7), the average value of SFI after one month was -64.4 points, and its increase to -45.4 points at the end of week 24 should be considered relatively reliable. Pairwise comparison of the averaged for all animals SFI values in the Sham and Sect, Sham and Raph, and Sect and Raph groups revealed significant differences at 4, 8, 12, 20, and 24 weeks after simulated injury. At 16 weeks post-intervention, the SFI values in the Sect and Raph groups were significantly different from those in the Sham group, but were not different from each other.

Conclusions. The method of determining the function of the paretic limb after sciatic nerve injury in rats using SFI has a number of technical limitations, which are the reason for significant variability in experimental results among different research groups. The reliable biphasic SFI dynamics that was discovered after sciatic nerve transection, as well as the insignificant (according to this data) fluctuations in SFI after sciatic nerve transection and neurorrhaphy, require independent verification, pathophysiological interpretation, and should be taken into account when evaluating rehabilitation methods using such an experimental model of peripheral nerve injury.

References

1. Kouyoumdjian JA. Peripheral nerve injuries: a retrospective survey of 456 cases. Muscle Nerve. 2006 Dec;34(6):785-8. [CrossRef] [PubMed]

2. Taylor CA, Braza D, Rice JB, Dillingham T. The incidence of peripheral nerve injury in extremity trauma. Am J Phys Med Rehabil. 2008 May;87(5):381-5. [CrossRef] [PubMed]

3. Scholz T, Krichevsky A, Sumarto A, Jaffurs D, Wirth GA, Paydar K, Evans GR. Peripheral nerve injuries: an international survey of current treatments and future perspectives. J Reconstr Microsurg. 2009 Jul;25(6):339-44. [CrossRef] [PubMed]

4. Antoniadis G, Kretschmer T, Pedro MT, König RW, Heinen CP, Richter HP. Iatrogenic nerve injuries: prevalence, diagnosis and treatment. Dtsch Arztebl Int. 2014 Apr 18;111(16):273- 9. [CrossRef] [PubMed] [PubMed Central]

5. Castillo-Galván ML, Martínez-Ruiz FM, de la Garza-Castro O, Elizondo-Omaña RE, Guzmán-López S. [Study of peripheral nerve injury in trauma patients]. Gac Med Mex. 2014 NovDec;150(6):527-32. Spanish. [PubMed]

6. Missios S, Bekelis K, Spinner RJ. Traumatic peripheral nerve injuries in children: epidemiology and socioeconomics. J Neurosurg Pediatr. 2014 Dec;14(6):688-94. [CrossRef] [PubMed]

7. Bekelis K, Missios S, Spinner RJ. Falls and peripheral nerve injuries: an age-dependent relationship. J Neurosurg. 2015 Nov;123(5):1223-9. [CrossRef] [PubMed]

8. Dalamagkas K, Tsintou M, Seifalian A. Advances in peripheral nervous system regenerative therapeutic strategies: A biomaterials approach. Mater Sci Eng C Mater Biol Appl. 2016 Aug 1;65:425-32. [CrossRef] [PubMed]

9. Zaidman M, Novak CB, Midha R, Dengler J. Epidemiology of peripheral nerve and brachial plexus injuries in a trauma population. Can J Surg. 2024 Jun 26;67(3):E261-E268. [CrossRef] [PubMed] [PubMed Central]

10. Jiang L, Jones S, Jia X. Stem Cell Transplantation for Peripheral Nerve Regeneration: Current Options and Opportunities. Int J Mol Sci. 2017 Jan 5;18(1). pii: E94. [CrossRef] [PubMed] [PubMed Central]

11. Tapp M, Wenzinger E, Tarabishy S, Ricci J, Herrera FA. The Epidemiology of Upper Extremity Nerve Injuries and Associated Cost in the US Emergency Departments. Ann Plast Surg. 2019 Dec;83(6):676-680. [CrossRef] [PubMed]

12. Kim SJ, Kwon YM, Ahn SM, Lee JH, Lee CH. Epidemiology of upper extremity peripheral nerve injury in South Korea, 2008 to 2018. Medicine (Baltimore). 2022 Dec 2;101(48):e31655. [CrossRef] [PubMed] [PubMed Central]

13. Murphy RNA, de Schoulepnikoff C, Chen JHC, Columb MO, Bedford J, Wong JK, Reid AJ. The incidence and management of peripheral nerve injury in England (2005-2020). J Plast Reconstr Aesthet Surg. 2023 May;80:75-85. [CrossRef] [PubMed]

14. Omid R, Stone MA, Zalavras CG, Marecek GS. Gunshot Wounds to the Upper Extremity. J Am Acad Orthop Surg. 2019 Apr 1;27(7):e301-e310. [CrossRef] [PubMed]

15. Baker HP, Straszewski AJ, Dahm JS, Dickherber JL, Krishnan P, Dillman DB, Strelzow JA. Gunshot-related lower extremity nerve injuries. Eur J Orthop Surg Traumatol. 2023 May;33(4):851-856. [CrossRef] [PubMed]

16. Dugom PM, Jester MP, Archie WH, Huynh DM, Scarcella JF, Guo Y. Outcomes in Ballistic Injuries to the Hand: Fractures and Nerve/Tendon Damage as Predictors of Poor Outcomes. Hand (N Y). 2024 May;19(3):382-386. [CrossRef] [PubMed] [PubMed Central]

17. Muss TE, Hu S, Bauder AR, Lin IC. The Epidemiology, Management, and Outcomes of Civilian Gunshot Wounds to the Upper Extremity at an Urban Trauma Center. Plast Reconstr Surg Glob Open. 2024 Apr 17;12(4):e5753. [CrossRef] [PubMed] [PubMed Central]

18. Aman M, Zimmermann KS, Thielen M, Thomas B, Daeschler S, Boecker AH, Stolle A, Bigdeli AK, Kneser U, Harhaus L. An Epidemiological and Etiological Analysis of 5026 Peripheral Nerve Lesions from a European Level I Trauma Center. J Pers Med. 2022 Oct 8;12(10):1673. [CrossRef] [PubMed] [PubMed Central]

19. Shaprynskyi Y, Lypkan V. Treatment of patients with gunshot traumatic amputations of the lower limbs due to explosive injury in the conditions of today’s war in Ukraine. Reports of Vinnytsia National Medical University. 2023;27:581-585. 10.31393/reports-vnmedical-2023-27(4)-08

20. Rosberg HE, Carlsson KS, Höjgård S, Lindgren B, Lundborg G, Dahlin LB. Injury to the human median and ulnar nerves in the forearm--analysis of costs for treatment and rehabilitation of 69 patients in southern Sweden. J Hand Surg Br. 2005 Feb;30(1):35-9. [CrossRef] [PubMed]

21. Immerman I, Price AE, Alfonso I, Grossman JA. Lower extremity nerve trauma. Bull Hosp Jt Dis (2013). 2014;72(1):43-52. Review. [PubMed]

22. Wali AR, Park CC, Brown JM, Mandeville R. Analyzing costeffectiveness of ulnar and median nerve transfers to regain forearm flexion. Neurosurg Focus. 2017 Mar;42(3):E11. [CrossRef] [PubMed]

23. Foster CH, Karsy M, Jensen MR, Guan J, Eli I, Mahan MA. Trends and Cost-Analysis of Lower Extremity Nerve Injury Using the National Inpatient Sample. Neurosurgery. 2019 Aug 1;85(2):250-256. [CrossRef] [PubMed]

24. Khalifeh JM, Dibble CF, Dy CJ, Ray WZ. Cost-Effectiveness Analysis of Combined Dual Motor Nerve Transfers versus Alternative Surgical and Nonsurgical Management Strategies to Restore Shoulder Function Following Upper Brachial Plexus Injury. Neurosurgery. 2019 Feb 1;84(2):362-377. [CrossRef] [PubMed]

25. Bergmeister KD, Große-Hartlage L, Daeschler SC, Rhodius P, Böcker A, Beyersdorff M, Kern AO, Kneser U, Harhaus L. Acute and long-term costs of 268 peripheral nerve injuries in the upper extremity. PLoS One. 2020 Apr 6;15(4):e0229530. [CrossRef] [PubMed] [PubMed Central]

26. Raizman NM, Endress RD, Styron JF, Emont SL, Cao Z, Park LI, Greenberg JA. Procedure Costs of Peripheral Nerve Graft Reconstruction. Plast Reconstr Surg Glob Open. 2023 Apr 10;11(4):e4908. [CrossRef] [PubMed] [PubMed Central]

27. Karsy M, Watkins R, Jensen MR, Guan J, Brock AA, Mahan MA. Trends and Cost Analysis of Upper Extremity Nerve Injury Using the National (Nationwide) Inpatient Sample. World Neurosurg. 2019 Mar;123:e488-e500. [CrossRef] [PubMed]

28. Hicks CW, Wang D, Matsushita K, Windham BG, Selvin E. Peripheral Neuropathy and All-Cause and Cardiovascular Mortality in U.S. Adults : A Prospective Cohort Study. Ann Intern Med. 2021 Feb;174(2):167-174. [CrossRef] [PubMed] [PubMed Central]

29. Trehan SK, Model Z, Lee SK. Nerve Repair and Nerve Grafting. Hand Clin. 2016 May;32(2):119-25. [CrossRef] [PubMed]

30. Melikov ZK, Medvediev VV. Peripheral nerve injury: molecular pathophysiology and prospects for restorative treatment by means of cell transplantation: a literature review. Ukr Neurosurg J. 2023Dec.26;29(4):3-12. [CrossRef]

31. Geuna S. The sciatic nerve injury model in pre-clinical research. J Neurosci Methods. 2015 Mar 30;243:39-46. [CrossRef] [PubMed]

32. Gordon T, Borschel GH. The use of the rat as a model for studying peripheral nerve regeneration and sprouting after complete and partial nerve injuries. Exp Neurol. 2017 Jan;287(Pt 3):331-347. [CrossRef] [PubMed]

33. Vela FJ, Martínez-Chacón G, Ballestín A, Campos JL, Sánchez-Margallo FM, Abellán E. Animal models used to study direct peripheral nerve repair: a systematic review. Neural Regen Res. 2020 Mar;15(3):491-502. [CrossRef] [PubMed] [PubMed Central]

34. Li A, Pereira C, Hill EE, Vukcevich O, Wang A. In Vitro, In Vivo and Ex Vivo Models for Peripheral Nerve Injury and Regeneration. Curr Neuropharmacol. 2022;20(2):344-361. [CrossRef] [PubMed] [PubMed Central]

35. Varier P, Raju G, Madhusudanan P, Jerard C, Shankarappa SA. A brief review of in vitro models for injury and regeneration in the peripheral nervous system. International Journal of Molecular Sciences. 2022 Jan 13;23(2):816. [CrossRef]

36. Evans PJ, Bain JR, Mackinnon SE, Makino AP, Hunter DA. Selective reinnervation: a comparison of recovery following microsuture and conduit nerve repair. Brain Res. 1991 Sep 20;559(2):315-21. [CrossRef] [PubMed]

37. Meyer RS, Abrams RA, Botte MJ, Davey JP, Bodine-Fowler SC. Functional recovery following neurorrhaphy of the rat sciatic nerve by epineurial repair compared with tubulization. J Orthop Res. 1997 Sep;15(5):664-9. [CrossRef] [PubMed]

38. Meek MF, Den Dunnen WF, Schakenraad JM, Robinson PH. Long-term evaluation of functional nerve recovery after reconstruction with a thin-walled biodegradable poly (DL-lactide-epsilon-caprolactone) nerve guide, using walking track analysis and electrostimulation tests. Microsurgery. 1999;19(5):247-53. [CrossRef] [PubMed]

39. Molotkovets VY, Medvediev VV, Korsak AV, Chaikovsky YuB, Tsymbaliuk VI. Restoration of the Integrity of a Transected Peripheral Nerve with the Use of an Electric Welding Technology. Neurophysiology. 2020;52, 31–42. [CrossRef]

40. Meder T, Prest T, Skillen C, Marchal L, Yupanqui VT, Soletti L, Gardner P, Cheetham J, Brown BN. Nerve-specific extracellular matrix hydrogel promotes functional regeneration following nerve gap injury. NPJ Regen Med. 2021 Oct 25;6(1):69. [CrossRef] [PubMed] [PubMed Central]

41. de Medinaceli L, Freed WJ, Wyatt RJ. An index of the functional condition of rat sciatic nerve based on measurements made from walking tracks. Exp Neurol. 1982 Sep;77(3):634-43. [CrossRef] [PubMed]

42. Wang T, Ito A, Aoyama T, Nakahara R, Nakahata A, Ji X, Zhang J, Kawai H, Kuroki H. Functional evaluation outcomes correlate with histomorphometric changes in the rat sciatic nerve crush injury model: A comparison between sciatic functional index and kinematic analysis. PLoS One. 2018 Dec 12;13(12):e0208985. [CrossRef] [PubMed] [PubMed Central]

43. Monte-Raso VV, Barbieri CH, Mazzer N, Yamasita AC, Barbieri G. Is the Sciatic Functional Index always reliable and reproducible? Journal of Neuroscience Methods. 2008;170(2):255-61. [CrossRef] [PubMed]

44. Tsymbaliuk VI, Medvediev VV, Ivanchov PV, Molotkovets VY, Chaikovsky YB, Korsak AV. [Electrical welding technology in restoring the integrity of the injured peripheral nerve: review of literature and own experimental research]. Ukr Neurosurg J. 2020;26(2):24-33 Ukrainian. [CrossRef]

45. Dellon ES, Dellon AL. Functional assessment of neurologic impairment: track analysis in diabetic and compression neuropathies. Plast Reconstr Surg. 1991 Oct;88(4):686-94. PubMed [PubMed]

46. Varejão AS, Meek MF, Ferreira AJ, Patrício JA, Cabrita AM. Functional evaluation of peripheral nerve regeneration in the rat: walking track analysis. J Neurosci Methods. 2001 Jul 15;108(1):1-9. Review. PubMed [PubMed]

47. Tsymbalyuk VI, Petriv TI, Molotkovets VY, Medvedev VV, Luzan BM, inventors; Bogomolets National Medical University, assignee. The device for conducting the "walk on the track" test. Patent of Ukraine 118157. 2017 July 27.

48. Rigoni M, Montecucco C. Animal models for studying motor axon terminal paralysis and recovery. Journal of Neurochemistry. 2017;142:122-9. [CrossRef] [PubMed]

49. Frigon A, Akay T, Prilutsky BI. Control of Mammalian Locomotion by Somatosensory Feedback. Compr Physiol. 2021 Dec 29;12(1):2877-2947. [CrossRef] [PubMed] [PubMed Central]

50. de Medinaceli L, DeRenzo E, Wyatt RJ. Rat sciatic functional index data management system with digitized input. Comput Biomed Res. 1984 Apr;17(2):185-92. [CrossRef] [PubMed]

51. Schiaveto de Souza A, da Silva CA, Del Bel EA. Methodological evaluation to analyze functional recovery after sciatic nerve injury. J Neurotrauma. 2004 May;21(5):627-35. [CrossRef] [PubMed]

52. Oliveira EF, Mazzer N, Barbieri CH, Selli M. Correlation between functional index and morphometry to evaluate recovery of the rat sciatic nerve following crush injury: experimental study. J Reconstr Microsurg. 2001 Jan;17(1):69-75. [CrossRef] [PubMed]

53. Abdallah I, Мedvediev V, Draguntsova N, Voitenko N, Tsymbaliuk V. Dependence of the restorative effect of Macroporous poly(N-[2-Hydroxypropyl]-methacrylamide hydrogel on the severity of experimental lacerative spinal cord injury. USMYJ. 2021 Dec. 26;127(4):8-21. [CrossRef]

54. Medvediev VV, Abdallah IM, Draguntsova NG, Savosko SI, Vaslovych VV, Tsymbaliuk VI, Voitenko NV. Model of spinal cord lateral hemi-excision at the lower thoracic level for the tasks of reconstructive and experimental neurosurgery. Ukr Neurosurg J. 2021Sep.27;27(3):33-5. [CrossRef]

55. Basso DM, Beattie MS, Bresnahan JC. A sensitive and reliable locomotor rating scale for open field testing in rats. J Neurotrauma. 1995 Feb;12(1):1-21. [CrossRef] [PubMed]

56. Dinh P, Hazel A, Palispis W, Suryadevara S, Gupta R. Functional assessment after sciatic nerve injury in a rat model. Microsurgery. 2009;29(8):644-9. [CrossRef] [PubMed]

57. Amniattalab A, Mohammadi R. Functional, Histopathological and Immunohistichemical Assessments of Cyclosporine A on Sciatic Nerve Regeneration Using Allografts: A Rat Sciatic Nerve Model. Bull Emerg Trauma. 2017 Jul;5(3):152-159. [PubMed] [PubMed Central]

58. Wall PD, Devor M, Inbal R, Scadding JW, Schonfeld D, Seltzer Z, Tomkiewicz MM. Autotomy following peripheral nerve lesions: experimental anaesthesia dolorosa. Pain. 1979 Oct;7(2):103-11. [CrossRef] [PubMed]

59. Coderre TJ, Grimes RW, Melzack R. Autotomy following sciatic and saphenous nerve sections - sparing of the medial toes after treatment of the sciatic-nerve with capsaicin. Experimental Neurology. 1986;91(2):355-65. [CrossRef] [PubMed]

60. Asato F, Butler M, Blomberg H, Gordh T. Variation in rat sciatic nerve anatomy: implications for a rat model of neuropathic pain. J Peripher Nerv Syst. 2000 Mar;5(1):19-21. [CrossRef] [PubMed]

61. Rupp A, Schmahl W, Lederer W, Matiasek K. Strain differences in the branching of the sciatic nerve in rats. Anat Histol Embryol. 2007 Jun;36(3):202-8. [CrossRef] [PubMed]

62. Ganguly A, McEwen C, Troy EL, Colburn RW, Caggiano AO, Schallert TJ, Parry TJ. Recovery of sensorimotor function following sciatic nerve injury across multiple rat strains. J Neurosci Methods. 2017 Jan 1;275:25-32. [CrossRef] [PubMed]

63. Jung Y, Ng JH, Keating CP, Senthil-Kumar P, Zhao J, Randolph MA, Winograd JM, Evans CL. Comprehensive evaluation of peripheral nerve regeneration in the acute healing phase using tissue clearing and optical microscopy in a rodent model. PLoS One. 2014 Apr 8;9(4):e94054. [CrossRef] [PubMed] [PubMed Central]

64. Terzis JK, Smith KJ. Repair of severed peripheral nerves: comparison of the "de Medinaceli" and standard microsuture methods. Exp Neurol. 1987 Jun;96(3):672-80. [CrossRef] [PubMed]

65. Sakuma M, Gorski G, Sheu SH, Lee S, Barrett LB, Singh B, Omura T, Latremoliere A, Woolf CJ. Lack of motor recovery after prolonged denervation of the neuromuscular junction is not due to regenerative failure. Eur J Neurosci. 2016 Feb;43(3):451-62. [CrossRef] [PubMed] [PubMed Central]

66. Goncharuk O, Savosko S, Petriv T, Tatarchuk M, Medvediev V, Tsymbaliuk V. Epineurial sutures, polyethylene glycol hydrogel and fibrin glue in the sciatic nerve repair in rats: functional and morphological assessments in experiment. Georgian Med News. 2020 Dec;(309):124-131. [PubMed]

67. Shenaq JM, Shenaq SM, Spira M. Reliability of sciatic function index in assessing nerve regeneration across a 1 cm gap. Microsurgery. 1989;10(3):214-9. [CrossRef] [PubMed]

68. Forman DS, Wood DK, DeSilva S. Rate of regeneration of sensory axons in transected rat sciatic nerve repaired with epineurial sutures. J Neurol Sci. 1979 Dec;44(1):55-9. [CrossRef] [PubMed]

69. Forman DS, Berenberg RA. Regeneration of motor axons in the rat sciatic nerve studied by labeling with axonally transported radioactive proteins. Brain Res. 1978 Nov 10;156(2):213-25. [CrossRef] [PubMed]

70. Navarro X, Verdú E, Butí M. Comparison of regenerative and reinnervating capabilities of different functional types of nerve fibers. Exp Neurol. 1994 Oct;129(2):217-24. [CrossRef] [PubMed]

71. Tessier-Lavigne M, Goodman CS. The molecular biology of axon guidance. Science. 1996 Nov 15;274(5290):1123-33. [CrossRef] [PubMed]

72. Breau MA, Trembleau A. Chemical and mechanical control of axon fasciculation and defasciculation. Semin Cell Dev Biol. 2023 May 15;140:72-81. [CrossRef] [PubMed]

Published

2024-12-30

How to Cite

Melikov, Z. K., & Medvediev, V. V. (2024). The rat’s sciatic nerve functional index dynamics after its transection and recovery by means of epineural neurorrhaphy. Ukrainian Neurosurgical Journal, 30(4), 30–42. https://doi.org/10.25305/unj.310430

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