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The effects of 4-aminopyridine and methylprednisolone on recovery of the facial nerve crush injury

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Abstract

Objective

4-Aminopyridine (4-AP) is a potassium channel blocker that enhances nerve excitability. In this study, rat models that have facial nerve crush injury (FNCI) were grouped and treated with methylprednisolone (MP), 4-AP, and a combination of these two drugs. Electrophysiologic and histopathologic outcomes of these groups will be compared with a control group.

Materials and methods

Thirty healthy male Wistar rats (mean weight of 265 g) were used in this study. The rats were randomly divided into five groups with six subjects in each: Group 1 (sham group), Group 2 (control group), Group 3 (MP group), Group 4 (4-aminopyridine group), and Group 5 (4-AP + MP group). All groups except the sham group underwent crush injury to the right facial nerve. Electrophysiologic and histologic recovery was recorded three weeks postoperatively.

Results

The 4-AP group and the combined group had a more significant recovery at Nerve Excitability Thresholds (NET) at the end of three weeks. The methylprednisolone group and the control group had a minimal recovery of NET. Histologically, when compared with the control group, the combined group was the only group that had significant recovery at all three of axonal degeneration, axon diameter, and myelin thickness.

Conclusion

In this experimental study, we demonstrated that a combination treatment of 4-AP and MP is more effective in the recovery of peripheric FNCI than in the no-treatment control group and in the 4-AP- or MP-alone groups. Moreover, our results suggested that 4-AP can be a potent alternative to MP in the treatment of the FNCI.

Level of evidence

N/A.

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References

  1. Lee LN, Lyford-Pike S, Boahene KDO (2013) Traumatic facial nerve injury. Otolaryngol Clin N Am 46(5):825–839. https://doi.org/10.1016/j.otc.2013.07.001

    Article  Google Scholar 

  2. Fisch U (1980) Management of intratemporal facial nerve injuries. J Laryngol Otol 94(1):129–134. https://doi.org/10.1017/s0022215100088575

    Article  CAS  PubMed  Google Scholar 

  3. Bajrović FF, Sketelj J, Jug M, Gril I, Mekjavić IB (2002) The effect of hyperbaric oxygen treatment on early regeneration of sensory axons after nerve crush in the rat. J Peripher Nerv Syst 7(3):141–148. https://doi.org/10.1046/j.1529-8027.2002.02020.x

    Article  PubMed  Google Scholar 

  4. Salinas RA, Alvarez G, Daly F, Ferreira J (2010) Corticosteroids for Bell’s palsy (idiopathic facial paralysis). Cochrane Database Syst Rev. 3:CD001942. https://doi.org/10.1002/14651858.CD001942.pub4

    Article  Google Scholar 

  5. Seth R, Revenaugh PC, Kaltenbach JA et al (2012) Facial nerve neurorrhaphy and the effects of glucocorticoids in a rat model. Otolaryngol Head Neck Surg 147(5):832–840. https://doi.org/10.1177/0194599812451551

    Article  PubMed  Google Scholar 

  6. Hall ED (1993) The effects of glucocorticoid and nonglucocorticoid steroids on acute neuronal degeneration. Adv Neurol 59:241–248

    CAS  PubMed  Google Scholar 

  7. Toros SZ, Karaca ÇT, Güneş P et al (2013) Hyperbaric oxygen versus steroid in facial nerve injury: an experimental animal study. Am J Otolaryngol 34(5):530–536. https://doi.org/10.1016/j.amjoto.2013.06.006

    Article  CAS  PubMed  Google Scholar 

  8. Rivera A, Raymond M, Grobman A, Abouyared M, Angeli SI (2017) The effect of n-acetyl-cysteine on recovery of the facial nerve after crush injury. Laryngoscope Investig Otolaryngol 2(3):109–112. https://doi.org/10.1002/lio2.68

    Article  PubMed  PubMed Central  Google Scholar 

  9. Tekdemir E, Tatlipinar A, Özbeyli D, Tekdemir Ö, Kınal E (2018) The effects of lipoic acid and methylprednisolone on nerve healing in rats with facial paralysis. Acta Otolaryngol 138(6):537–541. https://doi.org/10.1080/00016489.2017.1420914

    Article  CAS  PubMed  Google Scholar 

  10. Brushart TM, Hoffman PN, Royall RM, Murinson BB, Witzel C, Gordon T (2002) Electrical stimulation promotes motoneuron regeneration without increasing its speed or conditioning the neuron. J Neurosci 22(15):6631–6638

    Article  CAS  Google Scholar 

  11. Sakuma M, Minev IR, Gribi S, Singh B, Woolf CJ, Lacour SP (2015) Chronic electrical nerve stimulation as a therapeutic intervention for peripheral nerve repair. Bioelectron Med 2(1):43–48. https://doi.org/10.15424/bioelectronmed.2015.00005

    Article  Google Scholar 

  12. Blight AR, Henney HR, Cohen R (2014) Development of dalfampridine, a novel pharmacologic approach for treating walking impairment in multiple sclerosis. Ann N Y Acad Sci 1329:33–44. https://doi.org/10.1111/nyas.12512

    Article  CAS  PubMed  Google Scholar 

  13. DeForge D, Nymark J, Lemaire E et al (2004) Effect of 4-aminopyridine on gait in ambulatory spinal cord injuries: a double-blind, placebo-controlled, crossover trial. Spinal Cord 42(12):674–685. https://doi.org/10.1038/sj.sc.3101653

    Article  CAS  PubMed  Google Scholar 

  14. Hayes KC (2004) The use of 4-aminopyridine (fampridine) in demyelinating disorders. CNS Drug Rev 10(4):295–316. https://doi.org/10.1111/j.1527-3458.2004.tb00029.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Blight AR (1989) Effect of 4-aminopyridine on axonal conduction-block in chronic spinal cord injury. Brain Res Bull 22(1):47–52. https://doi.org/10.1016/0361-9230(89)90126-3

    Article  CAS  PubMed  Google Scholar 

  16. Bostock H, Sears TA, Sherratt RM (1981) The effects of 4-aminopyridine and tetraethylammonium ions on normal and demyelinated mammalian nerve fibres. J Physiol (Lond) 313:301–315. https://doi.org/10.1113/jphysiol.1981.sp013666

    Article  CAS  PubMed Central  Google Scholar 

  17. Tseng K-C, Li H, Clark A et al (2016) 4-Aminopyridine promotes functional recovery and remyelination in acute peripheral nerve injury. EMBO Mol Med 8(12):1409–1420. https://doi.org/10.15252/emmm.201506035

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Kahraman E, Yetiser S, Ozdag F (2020) Time dependent electrophysiological changes in nerve-crush traumatic facial nerve ınjury in rats. J Int Adv Otol 2020:7

    Google Scholar 

  19. Capacio BR, Byers CE, Matthews RL, Chang F-CT (1996) A Method for Determining 4-Aminopyridine in Plasma: Pharmacokinetics in Anaesthetized Guinea Pigs after Intravenous Administration. Biomed Chromatogr 10(3):111–116. https://doi.org/10.1002/(SICI)1099-0801(199605)10:3%3c111::AID-BMC569%3e3.0.CO;2-E

    Article  CAS  PubMed  Google Scholar 

  20. Jang CH, Cho YB, Choi CH, Jang YS, Jung W-K (2014) Effect of topical dexamethasone in reducing dysfunction after facial nerve crush injury in the rat. Int J Pediatr Otorhinolaryngol 78(6):960–963. https://doi.org/10.1016/j.ijporl.2014.03.025

    Article  PubMed  Google Scholar 

  21. Karlidag T, Yildiz M, Yalcin S, Colakoglu N, Kaygusuz I, Sapmaz E (2012) Evaluation of the effect of methylprednisolone and N-acetylcystein on anastomotic degeneration and regeneraton of the facial nerve. Auris Nasus Larynx 39(2):145–150. https://doi.org/10.1016/j.anl.2011.03.004

    Article  PubMed  Google Scholar 

  22. Cayli SR, Kocak A, Yilmaz U et al (2004) Effect of combined treatment with melatonin and methylprednisolone on neurological recovery after experimental spinal cord injury. Eur Spine J 13(8):724–732. https://doi.org/10.1007/s00586-003-0550-y

    Article  PubMed  PubMed Central  Google Scholar 

  23. Haghighi SS, Pugh SL, Perez-Espejo MA, Oro JJ (1995) Effect of 4-aminopyridine in acute spinal cord injury. Surg Neurol 43(5):443–447. https://doi.org/10.1016/0090-3019(95)80087-w

    Article  CAS  PubMed  Google Scholar 

  24. Beck R, Günther LC, Xiong G, Potschka H, Zwergal A (2014) The mixed blessing of treating symptoms in acute vestibular failure—evidence from a 4-aminopyridine experiment. Exper Neurol. https://doi.org/10.1016/j.expneurol.2014.08.013

    Article  Google Scholar 

  25. Jensen HB, Ravnborg M, Dalgas U, Stenager E (2014) 4-Aminopyridine for symptomatic treatment of multiple sclerosis: a systematic review. Ther Adv Neurol Disord 7(2):97–113. https://doi.org/10.1177/1756285613512712

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Dunn J, Blight A (2011) Dalfampridine: a brief review of its mechanism of action and efficacy as a treatment to improve walking in patients with multiple sclerosis. Curr Med Res Opin 27(7):1415–1423. https://doi.org/10.1185/03007995.2011.583229

    Article  CAS  PubMed  Google Scholar 

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Funding

Fatih Sultan Mehmet Education and Research Hospital, Istanbul, Turkey.

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Correspondence to Murat Toraman.

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There are no conflicts of interests or financial disclosures to report.

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This study was approved by the Marmara University Local Ethics Committee for Animal Experiments and performed at the Marmara University School of Medicine, Experimental Animal Laboratory, Istanbul, Turkey.

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Toraman, M., Külekçi Öztürk, S., Uslu Coşkun, B. et al. The effects of 4-aminopyridine and methylprednisolone on recovery of the facial nerve crush injury. Eur Arch Otorhinolaryngol 278, 3057–3063 (2021). https://doi.org/10.1007/s00405-020-06483-w

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  • DOI: https://doi.org/10.1007/s00405-020-06483-w

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