Investigating Lung Injury After Cervical Spinal Cord Injury

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Project Summary and Abstract In early 2019, the NIH sponsored meeting, NIH 2020: Launching a Decade for Disruption in Spinal Cord Injury (SCI) Research, brought together those living with SCI, clinicians, and basic science researchers. Together, they discussed the priorities and needs for SCI research. One major take home message was the critical desire for more studies geared towards investigating approaches which can significantly improve the quality of life of the SCI community beyond “home runs” like improving motor and sensory function. With this in mind, this proposal seeks to understand the mechanisms behind acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) after cervical SCI - where most SCIs occur and which leads to impaired respiratory motor function. ALI and ARDS significantly impacts those living with SCI by lowering their quality of life and decreasing their mortality. This is especially relevant now considering the current times of the SARS-CoV- 2/COVID-19 pandemic and its impact on lung health even in non-SCI individuals. Undoubtedly, this is a significant issue for this population severely impacting their lives. Towards this goal, we propose the following specific aims: Specific Aim 1: Test the hypothesis that cervical SCI leads to lung injury and alterations in lung metabolism. These experiments will help answer questions about the severity, temporal dynamics, and the mechanical, inflammatory, and metabolic profile of lung injury after cervical SCI. In Specific Aim 2, we will test the hypothesis that restoring diaphragmatic function after cervical SCI ameliorates ALI. These experiments will help determine the role impaired breathing plays in ALI and ARDS development after SCI and can it be prevented or reduced if we restore breathing function. Collectively, this proposal will elucidate the extent to which SCI can negatively impact lung health (mechanically, physiologically, and metabolically). Moreover, we will uncover the extent to which promising experimental therapeutic approaches can reverse or ameliorate these conditions. These are critical experiments which can help realize the overall goal of improving the quality of life and mortality of the SCI population.