Investigating the Effects of Brief Electrical Stimulation Duration on Sciatic Nerve Regeneration and Functional Recovery in a Rat Transection Model

Document Type : Original Paper

Authors

1 Electrical Engineering Department, Faculty of Engineering, Ferdowsi University of Mashhad, Mashhad, Iran.

2 Biology Department, Faculty of Sciences, Ferdowsi University of Mashhad, Mashhad, Iran.

Abstract

Introduction: Periodic and brief electrical stimulations (ES) are used as therapeutic protocols to improve nerve regeneration and functional recovery in various nervous system disorders. Periodic ES is applied transcutaneously for several sessions post-surgery, but brief ES is applied directly to the nerve during the surgery. Brief ES has no negative effects on functional recovery but applying periodic ES may delay the recovery. In most research studies, brief ES has been applied for 1-hour, although in some studies shorter durations were used. In this research, to reduce the risk of infection and cost, brief ESs with different durations (1-hour and shorter durations) were studied in a comparative study.
Material and Methods: The right sciatic nerve of 24 adult male Wistar rats was transected and sutured to a silicone tube. Experimental groups were stimulated by 10, 30, and 60 minutes ES (20Hz, 3V, 100µs). The hot plate test was done biweekly. At the end of the experimental period (12 weeks), the histomorphometric assessments were performed on the intra silicon tube segment of the regenerated nerve and its tibial branch.
Results: Hot plate test results showed an increase in the regeneration speed in experimental groups; furthermore, the 60-min ES group had better outcomes in histomorphometric assessment than other groups that may be due to the ES effect on the neuronal cell bodies.
Conclusion. As the results indicate, the 60-min ES had a better outcome compared to other groups. Other specifics of a brief ES such as frequency, pulse width, and waveform (monophasic or biphasic) may be studied in future research.

Keywords

Main Subjects


  1. Noble J, Munro CA, Prasad VS, Midha R. Analysis of upper and lower extremity peripheral nerve injuries in a population of patients with multiple injuries. J Trauma Acute Care Surg. 1998 Jul 1;45(1):116-22.
  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 1;87(5):381-5.
  3. Diao E, Vannuyen T. Techniques for primary nerve repair. Hand Clin. 2000 Feb 1;16(1):53.
  4. Trumble TE, Shon FG. The physiology of nerve transplantation. Hand Clin. 2000 Feb 1;16(1):105-22.
  5. Tohill M, Mantovani C, Wiberg M, Terenghi G. Rat bone marrow mesenchymal stem cells express glial markers and stimulate nerve regeneration. Neurosci. Lett. 2004 May 27;362(3):200-3.
  6. Javeed S, Faraji AH, Dy C, Ray WZ, MacEwan MR. Application of Electrical Stimulation for Peripheral Nerve Regeneration: Stimulation Parameters and Future Horizons. Interdiscip Neurosurg. 2021 Feb 9:101117.
  7. 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.
  8. Power HA, Morhart MJ, Olson JL, Chan KM. Postsurgical electrical stimulation enhances recovery following surgery for severe cubital tunnel syndrome: a double-blind randomized controlled trial. J Neurosurg. 2020 Jun 1;86(6):769-77.
  9. Al‐Majed AA, Brushart TM, Gordon T. Electrical stimulation accelerates and increases expression of BDNF and trkB mRNA in regenerating rat femoral motoneurons. Eur. J. Neurosci. 2000 Dec 1;12(12):4381-90.
  10. Al-Majed AA, Neumann CM, Brushart TM, Gordon T. Brief electrical stimulation promotes the speed and accuracy of motor axonal regeneration. J. Neurosci. 2000 Apr 1;20(7):2602-8.
  11. Brushart TM, Hoffman PN, Royall RM, Murinson BB, Witzel C, Gordon T. Electrical stimulation promotes motoneuron regeneration without increasing its speed or conditioning the neuron. J. Neurosci. 2002 Aug 1;22(15):6631-8.
  12. Calvey C, Zhou W, Stakleff KS, Sendelbach-Sloan P, Harkins AB, Lanzinger W, et al. Short-term electrical stimulation to promote nerve repair and functional recovery in a rat model. J Hand Surg. 2015 Feb 1;40(2):314-22.
  13. Han N, Xu C-g, Wang T-b, Kou Y-h, Yin X-f, Zhang P-x, et al. Electrical stimulation does not enhance nerve regeneration if delayed after sciatic nerve injury: the role of fibrosis. Neural Regen Res. 2015 Jan 1;10(1):90.
  14. Huang J, Zhang Y, Lu L, Hu X, Luo Z. Electrical stimulation accelerates nerve regeneration and functional recovery in delayed peripheral nerve injury in rats. Eur. J. Neurosci. 2013 Dec 1;38(12):3691-701.
  15. Wan L, Zhang S, Xia R, Ding W. Short‐term low‐frequency electrical stimulation enhanced remyelination of injured peripheral nerves by inducing the promyelination effect of brain‐derived neurotrophic factor on Schwann cell polarization. J. Neurosci. Res. 2010 Sep 1;88(12):2578-87.
  16. Xu C, Kou Y, Zhang P, Han N, Yin X, Deng J, et al. Electrical stimulation promotes regeneration of defective peripheral nerves after delayed repair intervals lasting under one month. PLoS One. 2014 Sep 2;9(9):e105045.
  17. Zhang X, Xin N, Tong L, Tong X-J. Electrical stimulation enhances peripheral nerve regeneration after crush injury in rats. Mol. Med. Rep. 2013 May 1;7(5):1523-7.
  18. Baptista AF, Gomes JR, Oliveira JT, Santos SM, Vannier‐Santos MA, Martinez AM. High‐and low‐frequency transcutaneous electrical nerve stimulation delay sciatic nerve regeneration after crush lesion in the mouse. J. Peripher. Nerv. Syst. 2008 Mar 1;13(1):71-80.
  19. Gigo‐Benato D, Russo TL, Geuna S, Domingues NRSR, Salvini TF, Parizotto NA. Electrical stimulation impairs early functional recovery and accentuates skeletal muscle atrophy after sciatic nerve crush injury in rats. Muscle & Nerve: Muscle Nerve. 2010 May 1;41(5):685-93.
  20. Lu M-C, Ho C-Y, Hsu S-F, Lee H-C, Lin J-H, Yao C-H, et al. Effects of electrical stimulation at different frequencies on regeneration of transected peripheral nerve. Neurorehabil Neural Repair. 2008 Jul 1;22(4):367-73.
  21. Lu M-C, Tsai C-C, Chen S-C, Tsai F-J, Yao C-H, Chen Y-S. Use of electrical stimulation at different current levels to promote recovery after peripheral nerve injury in rats. J Trauma Acute Care Surg. 2009 Nov 1;67(5):1066-72.
  22. Geremia NM, Gordon T, Brushart TM, Al-Majed AA, Verge VM. Electrical stimulation promotes sensory neuron regeneration and growth-associated gene expression. Exp Neurol. 2007 Jun 1;205(2):347-59.
  23. Alrashdan MS, Park J-C, Sung M-A, Yoo SB, Jahng JW, Lee TH, et al. Thirty minutes of low intensity electrical stimulation promotes nerve regeneration after sciatic nerve crush injury in a rat model. Acta Neurol Belg. 2010 Jun 1;110(2):168-79.
  24. Nasseri S, Naghavi N, Samaram H, Behnam Rassouli M. Investigating Effects of Electrical Stimulation on Sciatic Nerve Regeneration after Transection Injury in Wistar Rats. 3rd International Congress on Biomedicine; 2019 Nov 10.
  25. Samaram H, Naghavi N, Nasseri S, Behnam Rassouli M. Effects of Brief Electrical Stimulation on Regeneration of Transected Sciatic Nerve. 24th Iranian & 3rd International Congress of Physiology and Pharmacology; 2019 Oct 30.
  26. Masters DB, Berde CB, Dutta SK, Griggs CT, Hu D, Kupsky W, Langer R. Prolonged regional nerve blockade by controlled release of local anesthetic from a biodegradable polymer matrix. Anesthesiology. 1993 Aug 1;79(2):340-6.
  27. Masters DB, Berde CB, Dutta S, Turek T, Langer R. Sustained local anesthetic release from bioerodible polymer matrices: a potential method for prolonged regional anesthesia. Pharm Res. 1993 Oct 1;10(10):1527-32.
  28. Menorca R, Fussell TS, Elfar JC. Nerve physiology: mechanisms of injury and recovery. Hand clin. 2013 Aug 1;29(3):317-30.
  29. Al-Majed AA, Tam SL, Gordon T. Electrical stimulation accelerates and enhances expression of regeneration-associated genes in regenerating rat femoral motoneurons. Cell Mol Neurobiol. 2004 Jun 1;24(3):379-402.
  30. Han S, Kim DH, Sung J, Yang H, Park JW, Youn I. Electrical stimulation accelerates neurite regeneration in axotomized dorsal root ganglion neurons by increasing MMP-2 expression. Biochem Biophys Res Commun. 2019 Jan 8;508(2):348-53.
  31. Shapira Y, Sammons V, Forden J, Guo GF, Kipp A, Girgulis J, et al. Brief electrical stimulation promotes nerve regeneration following experimental in-continuity nerve injury. J Neurosurg. 2019 Jul 1;85(1):156-63.
  32. Koo J, MacEwan MR, Kang S-K, Won SM, Stephen M, Gamble P, et al. Wireless bioresorbable electronic system enables sustained nonpharmacological neuroregenerative therapy. Nat Med. 2018 Dec 1;24(12):1830-6.
  33. MacEwan MR, Gamble P, Stephen M, Ray WZ. Therapeutic electrical stimulation of injured peripheral nerve tissue using implantable thin-film wireless nerve stimulators. J Neurosurg. 2018 Feb 9;130(2):486-95.
  34. Fu SY, Gordon T. The cellular and molecular basis of peripheral nerve regeneration. Mol Neurobiol. 1997 Feb 1;14(1-2):67-116.
  35. Pearson K, Fouad K, Misiaszek J. Adaptive changes in motor activity associated with functional recovery following muscle denervation in walking cats. J Neurosurg. 1999 Jul 1;82(1):370-81.