Investigating Lung Injury After Cervical Spinal Cord Injury

R21: Investigating lung injury after cervical spinal cord injury Abstract More than 50% of spinal cord injuries (SCI) are at the cervical level and can result in the inability to breathe. Those injured are usually reliant on a mechanical ventilator in order to survive, which severely diminishes their quality of life and dramatically increases the demand for specialized health care and management. Not surprisingly, a common and highly significant comorbidity of SCI, especially at the cervical level, is acute lung injury (ALI) that can develop into the more severe form acute respiratory distress syndrome (ARDS). Indeed, the human cervical SCI population are more susceptible to death related to insufficient breathing and lung incapacitation or disease. This is especially relevant now considering the current environment of the coronavirus/COVID-19 pandemic. However, there have been remarkable findings in preclinical animal models suggesting that recovery of breathing is possible. Despite these advances, the impact of these promising interventions on comorbidities, including ALI and ARDS, is unknown. To overcome this gap in knowledge, we propose to investigate lung health and metabolic function, as well as after therapeutic treatments, in a well-defined animal model of cervical injury. Results from our laboratory have suggested that following experimental cervical SCI, in addition to paralysis of the diaphragm, there is a profound development of lung injury evidenced by increased edema, immune cell (including neutrophils) infiltration into the lungs, and heightened expression of inflammatory cytokines which mirrors the human clinical condition. Importantly, therapeutic options have been developed which can robustly restore diaphragmatic function, including the degradation of inhibitory extracellular matrix molecules, increasing respiratory drive, and the promotion of spinal cord plasticity. However, the impact of these strategies on preventing or ameliorating ALI and ARDS after injury is not known. This is the goal of this grant application. Collectively, based on our combined expertise in cervical SCI and treatment strategies, as well as ALI/ARDS and lung metabolism, make us the ideal team to investigate and answer these critical questions.