Defining recurrent laryngeal nerve injury in a mouse model for regenerative therapeutic investigations

Abstract

Injury of the recurrent laryngeal nerve (RLN), a branch of the vagus nerve, results in ipsilateral vocal fold (VF) paralysis that contributes to dysphagia, dysphonia, and dyspnea (i.e., swallow, vocal, and respiratory dysfunction, respectively). Unfortunately, there is no clinical intervention that will reliably restore physiologic movement to the VF after an RLN injury. Throughout this work, the effects of RLN injury on murine VF motion, swallowing behavior, vocalization production, and respiratory function are examined. Furthermore, methods for refining the functional assays used to assess these behaviors are developed, allowing for the production of more reliable and translatable results. Therefore, in Chapter 2, the effects of RLN injury are explored to confirm the fidelity of the laryngeal innervation pattern and functional outcomes (for vocal fold motion and swallowing) between mice and humans. In Chapter 3, an automated VF tracking and quantification software is developed to objectively measure dynamic VF motion, which is further refined in Chapter 4. Also in Chapter 4, we expand our translational mouse model to characterize swallow, vocal, and respiratory function in mice with unilateral VF paralysis following RLN injury. Lastly, VNS and its role as a therapeutic intervention for RLN injury is studied (Chapter 2), as well as the potential off-target effects this therapy may have on the many other organ systems provided innervation by the vagus nerve (Chapter 5). In conclusion, this work aims to provide a refined and reproducible animal model for researchers to use to investigate RLN pathophysiology and treatment options.