Mechanisms of swallowing dysfunction in a translational rodent model of chronic cervical spinal cord injury

The University of Florida's Division of Sponsored Research received a $408,750 project grant from the National Institute of Child Health and Human Development (NICHD) under the Child Health and Human Development Extramural Research program (CFDA 93.865), awarded on August 1, 2025, with completion targeted for July 31, 2027. This award funds investigator-initiated research examining the mechanisms of swallowing dysfunction in chronic cervical spinal cord injury (SCI) using a translational rodent model.

The research will characterize the development and progression of upper airway dysfunction from acute to chronic phases of cervical SCI, specifically utilizing a C4 contusion model. Key deliverables include assessment of time-dependent changes in swallow function, evaluation of neurochemical profile changes in upper airway motor neurons, and identification of functional swallowing impairments and aspiration mechanisms that differ between acute and chronic injury phases. This foundational research is designed to identify therapeutic targets for mitigating dysphagia and improving respiratory outcomes in individuals with chronic SCI, addressing a critical health concern where pneumonia accounts for 65% of deaths among those with high cervical injuries (C1-C4).

Abstract

Swallowing is a complex motor behavior that relies on rapid, precise coordination between the respiratory and swallowing pathways to protect the airway. Even minor disruptions in this coordination can result in dysphagia, which significantly increases the risk of aspiration pneumonia-a leading cause of death among individuals with neurological disorders. Dysphagia is especially concerning in those with spinal cord injury (SCI), where pneumonia is responsible for 65% of deaths in individuals with high cervical injuries (C1-C4). While dysphagia is often considered a transient issue following acute SCI, emerging evidence from both animal and human studies suggests IT may persist into the chronic phase, potentially contributing to silent aspiration and elevated morbidity. The fundamental goal of this project is to redefine our understanding of dysphagia following SCI by investigating the progression and underlying mechanisms of upper airway dysfunction in SCI. Specifically, we aim to characterize the development and extent of upper airway dysfunction from acute to chronic phases of cervical SCI using a clinically relevant rodent model of SCI (C4 contusion). Through this model, we will evaluate how changes in the neurochemical profile of upper airway motor neurons may underpin the persistence of dysfunction over time. Additionally, we will explore the mechanisms by which chronic SCI contributes to functional swallowing impairments and aspiration, which seem to differ from those observed in the acute injury phase. Utilizing a well-established C4 contusion model of SCI, we will assess time-dependent changes in swallow function and neural circuit reorganization. This research will lay essential groundwork for future studies aimed at identifying therapeutic targets to mitigate dysphagia and improve respiratory outcomes for individuals with chronic SCI. Moreover, our findings may have broader implications for other neurological conditions with high dysphagia and aspiration rates, including traumatic brain injury and stroke.