A Novel Animal Model of Dysphagia Following Stroke

Abstract

Patients who have an ischemic stroke are at high risk of swallowing disorders. Aspiration due to swallowing disorders, specifically delayed trigger of the pharyngeal stage of swallowing, predisposes such patients to pneumonia. In the present study, we evaluated swallowing reflex in a rat model of transient middle cerebral artery occlusion (tMCAO), which is one of the most common experimental animal models of cerebral ischemia, in order to develop a novel animal model of dysphagia following ischemic stroke. A swallowing reflex was elicited by a 10-s infusion of distilled water (DW) to the pharyngolaryngeal region in the tMCAO rat model. Swallowing reflex was estimated using the electromyographic activity of the mylohyoid muscle from 1 to 3 weeks after surgery. Two weeks after tMCAO, the number of swallows significantly decreased and the onset latency of the first swallow was prolonged compared with that of the sham group. The number of swallows in rats significantly increased by infusions of 10 mM citric acid and 0.6 μM capsaicin to the pharyngolaryngeal region compared with the number from infusion of DW. It has been reported that sensory stimulation of the pharyngolaryngeal region with citric acid, capsaicin, and L-menthol ameliorates hypofunction of pharyngeal-stage swallowing in dysphagia patients. Therefore, the tMCAO rat model may show some of the symptoms of pharyngeal-stage swallowing disorders, similar to those in patients with ischemic stroke. This rat tMCAO model has the potential to become a novel animal model of dysphagia following stroke that is useful for development of therapeutic methods and drugs.

Adapting Human Videofluoroscopic Swallow Study Methods to Detect and Characterize Dysphagia in Murine Disease Models

“…However, only three murine disease models have been specifically investigated relative to dysphagia: a mouse model of ALS 13,14 and rat models of Parkinson's disease 12,15-17 and stroke 18 . Each of these preliminary studies utilized different methodologies to assess dysphagia, rendering it impossible to derive meaningful comparisons between species and diseases.…”

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

“…There are multiple models of Parkinson’s disease, including (6-OHDA)-induced DA depletion [8, 37], surgical lesions [42] and PINK KO genetic models [22, 23]. Surgical or pharmacological models of stroke in rodents have been common, but are now being developed and validated for examining dysphagia [19, 44]. Injuries that are associated with dysphagia, such as damage to branches of the vagus nerve, recurrent or superior laryngeal nerve [11, 12, 16, 38], or other sensory deficits [18], can be relatively easily duplicated in animal models.…”

Establishment and Effects of Ginger and Kikyoto of a Haloperidol-Induced Dysphagia Model in Guinea Pigs

“…Similar to capsaicin, 6-gingerols are vanilloid receptor 1 agonists [27]. Vanilloid receptor 1 regulates swallowing, and administration of capsaicin improves dysphagia in elderly people and rats with dysphagia induced by middle cerebral artery occlusion [7] [28] [29]. Additionally, it has been reported that gingerol promotes swallowing in young adult women [17].…”

“…We investigated the swallowing ability of the guinea pigs with videofluoroscopic examination. We evaluated frequency of the deglutition as the outcome measure of the ability of the deglutition as described previously [7]. The ratio of BaSO 4 to glucose in the contrast medium was 5:2 (n = 2).…”

“…Several compounds were suggested to improve dysphagia [4]- [6]; however, no available medicine treats dysphagia fundamentally. To date, few studies report about animal models of dysphagia [7]. Therefore, animal models of swallowing dysfunction are required to develop novel therapeutic drugs for the treatment of dysphagia.…”