Spinal cord injuries have a significant and far-reaching impact, affecting more than 300,000 people in the United States alone. Among these injuries, cervical-level injuries are the most common, accounting for approximately 60% of all spinal cord injuries. Pulmonary complications, specifically aspiration-related pneumonia, rank as the primary cause of death in individuals with these injuries. Notably, those with cervical spinal cord injuries have an elevated risk of experiencing acute lung injury and acute respiratory distress syndrome. Moreover, spinal cord injuries, regardless of their location, often lead to gastric dysmotility, a condition frequently linked with gastroesophageal reflux disease. This research aims to untangle the intricate relationship between these interconnected health issues and their collective impact on pulmonary function. Here we tested the hypotheses 1) that cervical spinal cord injury increases the susceptibility for developing acute lung injury associated with gastric juice aspiration and 2) that TRPV4 inhibitors will mitigate gastric fluid/SCI-induced lung injury. These studies employed a rat model of spinal cord injury, C2 hemisection (C2Hx). This model mimics the reduced inspiratory tidal volume observed in individuals with cervical spinal cord injuries and has more recently been shown to recapitulate certain aspects of lung injury associated with spinal cord injuries. Additionally, to produce the effects of gastric reflux, gastric juices were introduced into the trachea in a subset of animals following spinal cord injury. Furthermore, TRPV4 inhibitors were administered to assess their potential to mitigate lung damage after spinal injury, gastric juice instillation or at both times. Preliminary data suggest that C2Hx and low levels of gastric juice increase inflammatory markers in the lung and circulation above even high levels of gastric instillation. Further, preliminary data supports the hypothesis that TRVP4 inhibition may protect the lung. The outcomes of these investigations will provide valuable insights into how spinal cord injuries might predispose individuals to lung injury. Additionally, they will evaluate the effcacy of a promising therapeutic approach using TRPV4 inhibitors to restore lung barrier function, potentially reversing this susceptibility. R21NS121966-01. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.