Establishment of a novel brainstem ischemic dysphagia model: single-cell sequencing reveals the molecular mechanisms underlying mPES intervention.

Abstract

OBJECTIVE: Previous animal models of post-stroke dysphagia (PSD) have limitations-these models are primarily induced by cortical strokes. Compared to cortical strokes, brainstem strokes are more likely to cause dysphagia, and the pathological mechanisms underlying dysphagia differ by focal infarction location. This study aimed to create a novel rat dysphagia model via brainstem ischemia (BSI) and explore modified pharyngeal electrical stimulation (mPES) therapy. METHODS: Rat brainstem ischemia was induced by photochemical embolization, confirmed by MRI and pathology. Swallowing function was assessed using Videofluoroscopic Swallowing Study (VFSS), while motor and neurobehavioral changes were evaluated through behavioral tests. Post-mPES treatment, VFSS was conducted to evaluate the swallowing function and single-cell transcriptomics was performed to explore therapeutic mechanisms. RESULTS: The BSI model showed stable dysphagia characteristics, with prolonged pharyngeal transit time, increased inter-swallowing interval and smaller bolus size area. mPES significantly improved these parameters. Behavioral tests revealed BSI caused anxiety-like behavior and worse motor performance in rats. Single-cell transcriptomics indicated mPES treatment involved multiple biological mechanisms, possibly exerting therapeutic effects by influencing oligodendrocyte differentiation and myelin, or synapse regeneration and repair. CONCLUSION: The novel BSI-induced dysphagia model exhibited stable swallowing function deficits. mPES effectively improved these deficiencies, with therapeutic mechanisms potentially associated with oligodendrocytes.