Investigating Lung Injury After Cervical Spinal Cord Injury

颈脊髓损伤后肺损伤的调查

• 批准号: 10204300
• 负责人: Warren Joseph Alilain
• 金额: $ 42.08万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10204300
• 关键词: 2019-nCoV; Acute; Acute Lung Injury; Address; Adult Respiratory Distress Syndrome; Animal Model; Animals; Basic Science; Breathing; COVID-19 pandemic; Cells; Cervical; Cervical spinal cord injury; Cessation of life; Chronic; Clinical; Communities; Deterioration; Development; Disease; Edema; Environment; Extracellular Matrix; Goals; Health; Histology; Home; Human; Immune; Impairment; Individual; Inflammation; Inflammatory; Injury; Intervention; Investigational Therapies; Ipsilateral; Knowledge; Laboratories; Lateral; Lung; Mechanical Ventilators; Mechanics; Metabolic; Metabolism; Mind; Motor; Neutrophil Infiltration; Periodicity; Physiological; Play; Population; Quality of life; Recovery; Research; Research Personnel; Respiratory Diaphragm; Respiratory Paralysis; Role; Running; Science; Sensory; Severities; Spinal Cord Plasticity; Spinal cord injury; Testing; Therapeutic; Time; United States National Institutes of Health; comorbidity; cytokine; experimental study; health management; improved; injured; lung development; lung injury; male; meetings; metabolic profile; metabolomics; mortality; motor recovery; pre-clinical; prevent; respiratory; restoration

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.

项目摘要和摘要 2019年初，NIH主办了一次会议，NIH 2020：启动脊柱颠覆十年 脊髓损伤(SCI)研究，汇集了脊髓损伤患者、临床医生和基础科学研究人员。 他们一起讨论了SCI研究的优先事项和需求。一个重要的带回家的信息是 迫切希望进行更多的研究，以便研究能够显着改善 除了本垒打之外，SCI社区的生活质量还包括改善运动和感觉功能。有了这一点 请记住，这项建议旨在了解急性肺损伤(ALI)和急性呼吸综合征(ALI)背后的机制 颈椎脊髓损伤后的窘迫综合征(ARDS)--大多数脊髓损伤都发生在那里，导致呼吸障碍 运动功能。ALI和ARDS通过降低SCI患者的生活质量和 降低他们的死亡率。考虑到SARS冠状病毒的当前时代，这一点尤其相关- 2/新冠肺炎大流行及其对肺健康的影响，即使是在非脊髓损伤患者中。毫无疑问，这是一场 对于这一人群来说，这是一个严重影响他们生活的重大问题。针对这一目标，我们提出如下建议 具体目标：具体目标1：检验颈椎脊髓损伤导致肺损伤和肺改变的假说 新陈代谢。这些实验将有助于回答有关严重程度、时间动力学和 颈椎脊髓损伤后肺损伤的机械、炎症和代谢特征。在具体目标2中，我们将测试 颈椎损伤后恢复横隔膜功能可改善ALI。这些实验将 帮助确定呼吸障碍在脊髓损伤后ALI和ARDS的发生中所起的作用 如果我们恢复呼吸功能，就可以预防或减少。总体而言，这项提案将阐明 哪些脊髓损伤会对肺健康产生负面影响(机械、生理和代谢方面)。此外，我们 将揭示有希望的实验性治疗方法可以逆转或改善的程度 这些条件。这些都是关键的实验，可以帮助实现改善 脊髓损伤人群的生活质量和死亡率。