Mechanisms of Lingual Motor Plasticity of Post-Stroke Dysphagia in an Animal Model

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Project Summary After stroke, up to 50% of people have difficulty swallowing, known as dysphagia. Post stroke dysphagia is a serious problem associated with poor outcomes including malnutrition, aspiration pneumonia, long-term care, and death. Clinical care is often limited to compensatory strategies due to a lack of evidence establishing any particular treatment as most beneficial. For recovering limb function after stroke, exercises are the primary rehabilitative approach and a great deal is known about aspects of corticospinal plasticity that contribute to recovery of function. Exercise approaches, such as tongue exercise, are also used in therapy for poststroke dysphagia. However, although tongue exercises have yielded positive results for post stroke dysphagia, much less is known about post stroke plasticity of the corticobulbar tract innervating the cranial muscles. Cranial muscle motor nuclei are located in the brainstem and generally receive much more bilateral innervation than limb muscles. Thus, the plastic mechanisms contributing to the recovery of swallowing function may differ substantially from limbs and must be understood to improve the clinical treatment of post stroke dysphagia. The proposed research will address this gap in knowledge by using a rat model of post stroke dysphagia, recently validated by Dr. Cullins, to establish plastic changes to the lingual cortex, brainstem, and muscles that occur after stroke and the impact of age and clinically based tongue exercise intervention on these mechanisms. The K99 phase will focus on lingual neuromuscular plasticity after stroke in young adult and aged rats. Aim 1: Quantify neuroplastic changes that impact lingual motor function after stroke in the rat by testing the hypotheses that: (A) tongue representation in the intact motor cortex will increase; (B) BDNF, a neurotrophin associated with plasticity, will be upregulated in the hypoglossal brainstem motor nuclei that innervate the tongue, and (C) and these plastic changes will correlate with lingual strength and swallowing function. Aim 2: Quantify the impact of age on neuromuscular plasticity and the recovery of swallowing function in a rat model of stroke. The training and research in the K99 phase will allow Dr. Cullins to begin to establish mechanisms of therapeutic interventions for post stroke dysphagia in the independent R00 phase, by determining the muscular, neural, and functional changes associated with tongue exercise. Aim 1: Quantify the contribution of muscular plasticity to the impact of tongue exercise on lingual strength and swallowing function. Aim 2: Determine the impact of tongue exercise on neuroplasticity and interactions between age and exercise. The proposed study will generate fundamental knowledge about corticobulbar plasticity after stroke including cortical, brainstem, and muscular changes related to dysphagia and the impact of age and tongue exercise. Animal studies can inform clinical research by narrowing the vast variable space of potential treatment paradigms including factors such as timing, dose, and combined treatments. This foundational work will allow future studies to optimize interventions and guide clinical research with a long-term goal to improve the clinical treatment of post stroke dysphagia.