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Erschienen in: Dysphagia 3/2020

06.08.2019 | Original Article

A Surgical Mouse Model for Advancing Laryngeal Nerve Regeneration Strategies

verfasst von: Alexis Mok, Jakob Allen, Megan M. Haney, Ian Deninger, Brayton Ballenger, Victoria Caywood, Kate L. Osman, Bradford Zitsch, Bridget L. Hopewell, Aaron Thiessen, Marlena Szewczyk, Daniel Ohlhausen, Christopher I. Newberry, Emily Leary, Teresa E. Lever

Erschienen in: Dysphagia | Ausgabe 3/2020

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Abstract

Iatrogenic recurrent laryngeal nerve (RLN) injury is a morbid complication of anterior neck surgical procedures. Existing treatments are predominantly symptomatic, ranging from behavioral therapy to a variety of surgical approaches. Though laryngeal reinnervation strategies often provide muscle tone to the paralyzed vocal fold (VF), which may improve outcomes, there is no clinical intervention that reliably restores true physiologic VF movement. Moreover, existing interventions neglect the full cascade of molecular events that affect the entire neuromuscular pathway after RLN injury, including the intrinsic laryngeal muscles, synaptic connections within the central nervous system, and laryngeal nerve anastomoses. Systematic investigations of this pathway are essential to develop better RLN regenerative strategies. Our aim was to develop a translational mouse model for this purpose, which will permit longitudinal investigations of the pathophysiology of iatrogenic RLN injury and potential therapeutic interventions. C57BL/6J mice were divided into four surgical transection groups (unilateral RLN, n = 10; bilateral RLN, n = 2; unilateral SLN, n = 10; bilateral SLN, n = 10) and a sham surgical group (n = 10). Miniaturized transoral laryngoscopy was used to assess VF mobility over time, and swallowing was assessed using serial videofluoroscopy. Histological assays were conducted 3 months post-surgery for anatomical investigation of the larynx and laryngeal nerves. Eight additional mice underwent unilateral RLN crush injury, half of which received intraoperative vagal nerve stimulation (iVNS). These 8 mice underwent weekly transoral laryngoscopy to investigate VF recovery patterns. Unilateral RLN injury resulted in chronic VF immobility but only acute dysphagia. Bilateral RLN injury caused intraoperative asphyxiation and death. VF mobility was unaffected by SLN transection (unilateral or bilateral), and dysphagia (transient) was evident only after bilateral SLN transection. The sham surgery group retained normal VF mobility and swallow function. Mice that underwent RLN crush injury and iVNS treatment demonstrated accelerated and improved VF recovery. We successfully developed a mouse model of iatrogenic RLN injury with impaired VF mobility and swallowing function that can serve as a clinically relevant platform to develop translational neuroregenerative strategies for RLN injury.
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Metadaten
Titel
A Surgical Mouse Model for Advancing Laryngeal Nerve Regeneration Strategies
verfasst von
Alexis Mok
Jakob Allen
Megan M. Haney
Ian Deninger
Brayton Ballenger
Victoria Caywood
Kate L. Osman
Bradford Zitsch
Bridget L. Hopewell
Aaron Thiessen
Marlena Szewczyk
Daniel Ohlhausen
Christopher I. Newberry
Emily Leary
Teresa E. Lever
Publikationsdatum
06.08.2019
Verlag
Springer US
Erschienen in
Dysphagia / Ausgabe 3/2020
Print ISSN: 0179-051X
Elektronische ISSN: 1432-0460
DOI
https://doi.org/10.1007/s00455-019-10045-6

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