Swallowing disorders (dysphagia) commonly occur after stroke. There are a wide variety of potential post stroke dysphagia interventions, yet no consensus on the optimal treatment exists. Because the tongue has a key role in generating pressures for bolus propulsion during the oropharyngeal swallow, tongue exercise is an intervention in current clinical use. Although tongue weakness has been found post stroke, and rehabilitation often focuses on the tongue, the impact of stroke on biological aspects of the lingual muscles is not known. The proposed research will address this gap in knowledge by using a rat model of stroke to assess alterations in the structure and biochemical properties of the lingual muscles. The widely used middle cerebral artery occlusion (MCAO) rat model of stroke approximates the most common type of stroke and has been shown to manifest swallowing deficits. Developing this model for the study of post stroke dysphagia will allow us to establish the effects of stroke on the lingual muscles, and lay the groundwork for future investigations on the mechanisms of therapeutic interventions for stroke patients with dysphagia. The proposed one-year study has two specific aims.
Aim 1 : To test the hypothesis that unilateral transient cerebral ischemia induces alterations in lingual muscle structure, specifically an increase in the proportion of fast myosin heavy chain (MyHC )isoforms and a decrease in muscle fiber size and number. In MCAO and sham control rats, muscle samples will be collected bilaterally from genioglossus, longitudinal, and transverse lingual muscles as well as a limb muscle control at 1 and 8 weeks after surgery. The MyHC isoform composition and muscle fiber size will be determined.
Aim 2 : To test the hypothesis that unilateral transient cerebral ischemia results in reduced tongue force and impaired swallowing. Maximum tongue pressing force and videofluoroscopy of feeding animals will be collected before MCAO surgery and at 1 and 8-week time points. Videofluoroscopy measurements will include swallowing rate, bolus speed, bolus size, compensatory movements and novel biomechanical analyses. The proposed one-year study will establish the effects of stroke on the lingual muscles and validate the MCAO rat model of stroke as a model of post stroke dysphagia, laying the groundwork for future investigation of the mechanisms of therapeutic interventions for stroke patients with dysphagia. This work is highly significant because post stroke dysphagia is associated with aspiration pneumonia, malnutrition, dehydration, and increased mortality. The optimal management of post stroke dysphagia is not known and there are no universally established medical treatments. This project will further the understanding of changes that occur in the lingual muscles and help guide clinical research by allowing focused hypotheses.

Public Health Relevance

Dysphagia in stroke patients is an understudied problem that results in increased mortality, malnutrition, dehydration, and reduced quality of life. This project will contribute fundamental knowledge on the mechanisms of tongue muscle dysfunction by assessing post stroke alterations in lingual muscle structure, biology, and function. Developing an animal model of post stroke dysphagia is the first step towards determining the mechanisms of clinical interventions, and has the long term potential to inform and optimize the evidence based treatment of post stroke dysphagia.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32HD094527-01A1
Application #
9539446
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Marden, Susan F
Project Start
2018-04-01
Project End
2019-03-31
Budget Start
2018-04-01
Budget End
2019-03-31
Support Year
1
Fiscal Year
2018
Total Cost
Indirect Cost
Name
University of Wisconsin Madison
Department
Surgery
Type
Schools of Medicine
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715