Hostname: page-component-586b7cd67f-dsjbd Total loading time: 0 Render date: 2024-11-28T00:07:00.575Z Has data issue: false hasContentIssue false
  • English
  • Français

Development and characterisation of an experimental recurrent laryngeal nerve injury model for the study of viral gene therapy

Published online by Cambridge University Press:  25 June 2007

K Fung ,
N D Hogikyan ,
S B Heavner ,
D Ekbom  and
E L Feldman
K Fung*
Affiliation:
Division of Head and Neck Oncology and Reconstructive Surgery, Department of Otolaryngology, University of Western Ontario, London, Ontario, Canada
N D Hogikyan
Affiliation:
Department of Otolaryngology-Head and Neck Surgery Ann Arbor, Michigan, USA
S B Heavner
Affiliation:
Department of Otolaryngology-Head and Neck Surgery Ann Arbor, Michigan, USA
D Ekbom
Affiliation:
Department of Otolaryngology-Head and Neck Surgery Ann Arbor, Michigan, USA
E L Feldman
Affiliation:
Department of Neurology, University of Michigan, Ann Arbor, Michigan, USA
*
Address for correspondence: Dr Kevin Fung, Assistant Professor, Department of Otolaryngology, Division of Head and Neck Oncology and Reconstructive Surgery, London Health Sciences Centre – Victoria Hospital, Room C3-100, 800 Commissioners Road East, London, Ontario, CanadaN6A 4G5. Fax: 519 685 8567 E-mail: [email protected]
Get access Rights & Permissions [Opens in a new window]

Abstract

Objectives:

To develop and characterise an experimental model of recurrent laryngeal nerve injury for the study of viral gene therapy.

Methods:

Twenty rats underwent unilateral recurrent laryngeal nerve injury. After vocal fold mobility was observed, larynges were serially sectioned, and immunohistochemical techniques were employed to stain for neurofilament and motor endplates in order for a blinded investigator to determine the percentage of nerve–endplate contact, as a histological indicator of an intact neuromuscular connection.

Results:

All animal procedures resulted in complete, ipsilateral vocal fold paralysis that recovered by three weeks. The mean nerve–endplate contact percentage was 11.6 per cent at one week, 53.9 per cent at two weeks, 88.6 per cent at three weeks, 81.7 per cent at four weeks and 86.6 per cent at five weeks. The differences between results at week one and week three were statistically significant (p < 0.01). The mean nerve–endplate contact percentage on the control side was 86.8 per cent.

Conclusions:

There was a dramatic, measurable decrease in nerve–endplate contact percentage following crush injury to the recurrent laryngeal nerve. Spontaneous recovery was observed by three weeks post-injury. This model will be used to investigate the potential therapeutic role of viral gene therapy for the treatment of recurrent laryngeal nerve injury.

Keywords

Vocal Cord ParalysisRecurrent Laryngeal NerveGene Therapy
Type
Main Article
Information
The Journal of Laryngology & Otology , Volume 122 , Issue 5 , May 2008 , pp. 500 - 505
Copyright
Copyright © JLO (1984) Limited 2007

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1 Eisele, D. Complications of thyroid surgery. In: Eisele, D, ed. Complications in Head and Neck Surgery. St Louis: Mosby Year Book, 2000;423–37Google Scholar
2 Zeitels, SM, Casiano, RR, Gardner, GM, Hogikyan, ND, Koufman, JA, Rosen, CA. Voice and Swallowing Committee, American Academy of Otolaryngology-Head and Neck Surgery. Management of common voice problems: Committee report. Otolaryngol Head Neck Surg 2002;126:333–48Google Scholar
3 Kang, UJ. Genetic modification of cells with retrovirus vectors for grafting into the central nervous system. In: Kaplitt, MG, Loewy, AD, eds. Viral Vectors: Gene Therapy and Neuroscience Applications. San Diego: Academic Press, 1995;211–37CrossRefGoogle Scholar
4 Ghadge, GD, Roos, RP, Kang, UJ, Wollmann, R, Fishman, PS, Kalynych, AM et al. CNS gene delivery by retrograde transport of recombinant replication-defective adenoviruses. Gene Ther 1995;2:132–7Google ScholarPubMed
5 Rubin, AD, Mobley, B, Hogikyan, ND, Bell, K, Sullivan, K, Boulis, N et al. Delivery of an adenoviral vector to the crushed recurrent laryngeal nerve. Laryngoscope 2003;113:985–9Google Scholar
6 Boulis, NM, Turner, DE, Dice, JA, Bhatia, V, Feldman, EL. Characterization of adenoviral gene expression in spinal cord after remote vector delivery. Neurosurgery 1999;45:131–8Google Scholar
7 Turner, DE, Noordmans, AJ, Feldman, EL, Boulis, NM. Remote adenoviral gene delivery to the spinal cord: contralateral delivery and reinjection. Neurosurgery 2001;48:1309–17Google Scholar
8 Boulis, NM, Noordmans, AJ, Feldman, EL, Imperiale, MJ. Adeno-associated viral gene expression in the adult rat spinal cord following remote vector delivery. Mol Ther 2000;1:S110–11Google Scholar
9 Boulis, NM, Bhatia, V, Anlar, B, Brindle, TI, Feldman, EL. Retrograde adenoviral gene delivery to rat spinal cord via sciatic nerve microinjection. Soc Neurosci Abstr 1998;24:1308Google Scholar
10 Rubin, AD, Hogikyan, ND, Sullivan, K, Boulis, N, Feldman, EL. Remote delivery of rAAV-GFP to the rat brainstem via the recurrent laryngeal nerve. Laryngoscope 2001;111:2041–5Google Scholar
11 Shiotani, A, O'Malley, BW Jr, Coleman, ME, Flint, PW. Human insulin-like growth factor 1 gene transfer into paralyzed rat larynx: single vs multiple injection. Arch Otolaryngol Head Neck Surg 1999;125:555–60CrossRefGoogle ScholarPubMed
12 Bridge, PM, Ball, DJ, Mackinnon, SE, Nakao, Y, Brandt, K, Hunter, DA et al. Nerve crush injuries – a model for axonotmesis. Exp Neurol 1994;127:284–90CrossRefGoogle Scholar
13 Baumgartner, BJ, Shine, HD. Permanent rescue of lesioned neonatal motoneurons and enhanced axonal regeneration by adenovirus-mediated expression of glial cell-line-derived neurotrophic factor. J Neurosci Res 1998;54:766–77Google Scholar
14 Park, HJ, Kim, HN, Kim, KM. Redistribution of facial nerve motor neurons after recovery from nerve crushing injury in the gerbil. Acta Otolaryngol 1995;115:273–5Google Scholar
15 Mu, L, Yang, S. An experimental study on the laryngeal electromyography and visual observations in varying types of surgical injuries to the unilateral recurrent laryngeal nerve in the neck. Laryngoscope 1991;101:699–708Google Scholar
16 van Lith-Bijl, JT, Mahieu, HF, Stolk, RJ, Tonnaer, JA, Groenhout, C, Konings, PN. Laryngeal abductor function after recurrent laryngeal nerve injury in cats. Arch Otolaryngol Head Neck Surg 1996;122:393–6CrossRefGoogle ScholarPubMed
17 Saito, K, Shiotani, A, Watabe, K, Moro, K, Fukuda, H, Ogawa, K. Adenoviral GDNF gene transfer prevents motoneuron loss in the nucleus ambiguus. Brain Res 2003;996:61–7Google Scholar
18 Araki, K, Shiotani, A, Watabe, K, Saito, K, Moro, K, Ogawa, K. Adenoviral GDNF gene transfer enhances neurofunctional recovery after recurrent laryngeal nerve injury. Gene Ther 2006;13:296–303CrossRefGoogle ScholarPubMed