A Surgical Mouse Model for Advancing Laryngeal Nerve Regeneration Strategies

A Mouse Model of Dysphagia After Facial Nerve Injury

“…Thus, it is logical to posit that facial nerve MT injury directly causes restricted hyoid movement, which indirectly hinders tongue movement. We recognize that this functional deficit may be more apparent in mice, with drinking/licking behavior requiring marked tongue protrusion that visibly elevates the hyoid bone and larynx in synchrony with each lick 43 …”

“…We recognize that this functional deficit may be more apparent in mice, with drinking/licking behavior requiring marked tongue protrusion that visibly elevates the hyoid bone and larynx in synchrony with each lick. 43 Alternatively, facial nerve MT injury may directly alter the brainstem central pattern generators (CPGs) for licking, chewing, and swallowing, each of which includes the facial motor nucleus that gives rise to CN VII. [67][68][69][70] In rodent models, CN VII transection results in 15% to 30% loss of ipsilateral facial motoneurons within 2 weeks postinjury, 71,72 which we speculate disrupts the upstream synaptic connections between the facial motor nucleus and the numerous CPG components (i.e., sensory and motor regions within the brainstem and brain) to cause the altered licking, chewing, and swallowing behaviors observed in our mice 2 weeks after MT transection.…”

“…[34][35][36][37] We chose the C57BL/6J mouse strain because it is the most commonly studied laboratory rodent in biomedical research, 38 and more specifically because it is an established model for investigating the neural control of normal swallowing 39,40 and the mechanisms of neurogenic dysphagia secondary to biological aging 40 and iatrogenic laryngeal nerve injury. [41][42][43] In this study, we compared swallowing outcomes in C57BL/6J mice after surgical transection of the MT versus the marginal mandibular branch (MMB) of the facial nerve. Transection injury (neurotmesis) was chosen for experimental replicability over the other two nerve injury types (neurapraxia and axonotmesis).…”

“…Here, we investigated the stereotypical oropharyngeal deglutitive behavior of mice before and after MT versus MMB transection, evaluated using our previously validated videofluoroscopic swallow study (VFSS) methodology. 39,40,43,62 Based on our previous work, we expected VFSS outcome measures would be altered in a predictable direction: MT injury would result in slower lick and swallow rates, longer inter-swallow intervals, and greater lick-swallow ratios (i.e., vallecular fill time), collectively indicative of oropharyngeal (i.e., oral and pharyngeal stage) dysphagia; MMB injury would result solely in slower lick rate (i.e., oral stage dysphagia). Although we expected that MT transection would produce a more robust model for translational investigations of dysphagia treatment discovery, we recognize the potential benefits of establishing an MMB injury model: elimination of morbidity associated with impaired eye blink and vibrissae movement and confounding stress-induced responses associated with frequent daily handling for application of ocular lubricant.…”

“…Here, we used videofluoroscopy, the clinical gold standard test for dysphagia diagnosis, 31–33 to investigate the effect of facial nerve injury on swallowing in mice, whose neural control of swallowing is remarkably similar to humans 34–37 . We chose the C57BL/6J mouse strain because it is the most commonly studied laboratory rodent in biomedical research, 38 and more specifically because it is an established model for investigating the neural control of normal swallowing 39,40 and the mechanisms of neurogenic dysphagia secondary to biological aging 40 and iatrogenic laryngeal nerve injury 41–43 …”