Animal Models for Dysphagia Studies: What Have We Learnt So Far

German, Rebecca Z.; Crompton, A. W.; Gould, François D. H.; Thexton, A.J.

doi:10.1007/s00455-016-9778-7

Cited by 47 publications

(46 citation statements)

References 51 publications

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“…Gould et al (23) found differences in tongue shape, tongue movement, and shape and size of the bolus. Finally, the relative timing of tongue movements changes with this lesion (19). The results presented in this paper reject the initial null hypothesis that the RLN lesion will only impact those imme-diate structures and fields that it supplies directly.…”

Section: Testing the Effect Of A Lesion Of The Rln On Swallowingsupporting

confidence: 54%

Impact of recurrent laryngeal nerve lesion on oropharyngeal muscle activity and sensorimotor integration in an infant pig model

DeLozier

Gould

Ohlemacher

et al. 2018

Journal of Applied Physiology

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The successful performance of a swallow requires dynamic integration between a wide range of sensory inputs and muscle activities to produce the coordinated kinematics of oropharyngeal structures. Damage to the recurrent laryngeal nerve (RLN) produces dysphagia in infants, with food or liquid entering the airway despite this nerve having minimal direct sensory or motor connections to the act of swallowing, apart from vocal fold closure. Previous results have demonstrated that a complete RLN lesion disrupts both performance and kinematics before initiation of the pharyngeal swallow in infants. We tested the hypothesis that a RLN lesion produces changes in the normal activity of oral floor, tongue, and infrahyoid muscles during a swallow. We recorded swallowing in our validated infant pig model, with synchronous high-speed imaging and fine-wire, chronic electromyography. We found changes in the timing, duration, and amplitude of the motor pattern in an array of muscles that are supplied by several different cranial and cervical nerves. Some of these changes in muscle activity are associated with the preparatory aspects of bolus aggregation or movement and so occur before the pharyngeal swallow. Taken with previous biomechanical results, these patterns suggest an intricate brain stem sensorimotor integration that occurs as part of a swallow. In particular, the execution of oral motor function is changed as a result of this simple lesion. NEW & NOTEWORTHY Damage to the recurrent laryngeal nerve compromises swallowing despite an absent or minimal contribution to either the motor or sensory aspects of this function. This study documents EMG changes, following RLN lesion, to non-RLN innervated muscles that are active during swallowing in an infant model. Some of these muscles fire before the pharyngeal swallow and are associated with the preparatory aspects of bolus aggregation and movement, suggesting important sensorimotor integration at a brain stem level.

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Section: Testing the Effect Of A Lesion Of The Rln On Swallowingsupporting

confidence: 54%

Impact of recurrent laryngeal nerve lesion on oropharyngeal muscle activity and sensorimotor integration in an infant pig model

DeLozier

Gould

Ohlemacher

et al. 2018

Journal of Applied Physiology

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“…Dysphagia research using animal models, including the Pink1 −/− model of PD, has the potential to shape practice and treatment in the human population [22]. The primary purpose of this study was to use videofluoroscopy to determine whether early oropharyngeal swallowing impairments are evident in the Pink1 −/− genetic rat model of PD and to relate these deficits to early neuropathological changes.…”

Section: Discussionmentioning

confidence: 99%

“…Consequently, studying humans in the prodromal period is often difficult due to methodological limitations. Thus, animal models of PD offer a means to circumvent these limitations in order to characterize underlying neuropathology, disease mechanisms, and identify potential treatments for dysphagia during the early stages of PD [20–22]. …”

Section: Introductionmentioning

confidence: 99%

Pink1 −/− Rats Show Early-Onset Swallowing Deficits and Correlative Brainstem Pathology

et al. 2018

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Parkinson disease (PD) compromises oropharyngeal swallowing, which negatively affects quality of life and contributes to aspiration pneumonia. Dysphagia often begins early in the disease process, and does not improve with standard therapies. As a result, swallowing deficits are undertreated in the PD population. The Pink1 −/− rat is used to model PD, and demonstrates widespread brainstem neuropathology in combination with early-onset sensorimotor dysfunction; however, to date, swallowing behaviors have not been evaluated. To test the hypothesis that Pink1 −/− rats demonstrate early-onset differences in swallowing, we analyzed within-subject oropharyngeal swallowing using videofluoroscopy. Pink1 −/− and wildtype (WT) controls at 4 (Pink1 −/− n = 16, WT = 16) and 8 (Pink1 −/− n = 12, WT = 12) months of age were tested. The average and maximum bolus size was significantly increased in Pink1 −/− rats at both 4 and 8 months. Bolus average velocity was increased at 8 months for all animals; yet, Pink1 −/− animals had significantly increased velocities compared to WT at 8 months. The data show a significant reduction in mastication rate for Pink1 −/− rats at 8 months suggesting the onset of oromotor dysfunction begins at this time point. Relationships among swallowing variables and neuropathological findings, such as increased alpha-synuclein protein in the nucleus ambiguus and reductions in noradrenergic cells in the locus coeruleus in the Pink1 −/− rats, were determined. The presence of early oropharyngeal swallowing deficits and relationships to brainstem pathology in Pink1−/− rat models of PD indicate that this may be a useful model of early swallowing deficits and their mechanisms. These findings suggest clinical implications for early detection and management of dysphagia in PD.

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“…Our work on SLN and RLN lesions shows how a strictly experimental, systematic, basic science approach can provide the framework for beginning to understand these issues (6,13,14,19,22,23). Animal model work is particularly wellsuited to the hierarchical study of insult, pathophysiology, and disease (41). Indeed, the literature on animal models of neurological disorders increasingly combines attempts to model the complete disorder with targeted approaches seeking to reproduce a particular part of the neurological disorder to test hypotheses about pathophysiology (42).…”

Section: A Better Etiology Of Dysphagia Is Needed One That Is Based mentioning

confidence: 99%

Specific Vagus Nerve Lesion Have Distinctive Physiologic Mechanisms of Dysphagia

et al. 2019

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Swallowing is complex at anatomical, functional, and neurological levels. The connections among these levels are poorly understood, yet they underpin mechanisms of swallowing pathology. The complexity of swallowing physiology means that multiple failure points may exist that lead to the same clinical diagnosis (e.g., aspiration). The superior laryngeal nerve (SLN) and the recurrent laryngeal nerve (RLN) are branches of the vagus that innervate different structures involved in swallowing. Although they have distinct sensory fields, lesion of either nerve is associated clinically with increased aspiration. We tested the hypothesis that despite increased aspiration in both case, oropharyngeal kinematic changes and their relationship to aspiration would be different in RLN and SLN lesioned infant pigs. We compared movements of the tongue and epiglottis in swallows before and after either RLN or SLN lesion. We rated swallows for airway protection. Posterior tongue ratio of safe swallows changed in RLN (p = 0.01) but not SLN lesioned animals. Unsafe swallows post lesion had different posterior tongue ratios in RLN and SLN lesioned animals. Duration of epiglottal inversion shortened after lesion in SLN animals (p = 0.02) but remained unchanged in RLN animals. Thus, although SLN and RLN lesion lead to the same clinical outcome (increased aspiration), the mechanisms of failure of airway protection are different, which suggests that effective therapies may be different with each injury. Understanding the specific pathophysiology of swallowing associated with specific neural insults will help develop targeted, disease appropriate treatments.

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Animal Models for Dysphagia Studies: What Have We Learnt So Far

Cited by 47 publications

References 51 publications

Impact of recurrent laryngeal nerve lesion on oropharyngeal muscle activity and sensorimotor integration in an infant pig model

Impact of recurrent laryngeal nerve lesion on oropharyngeal muscle activity and sensorimotor integration in an infant pig model

Pink1 −/− Rats Show Early-Onset Swallowing Deficits and Correlative Brainstem Pathology

Specific Vagus Nerve Lesion Have Distinctive Physiologic Mechanisms of Dysphagia

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