Neonatal inflammation impairs control of breathing

新生儿炎症损害呼吸控制

• 批准号: 10378435
• 负责人: Adrianne Genest Huxtable
• 金额: $ 7.59万
• 依托单位: UNIVERSITY OF OREGON
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-06-01 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10378435
• 关键词: Acute; Adult; Anti-Inflammatory Agents; Applications Grants; Area; Award; Behavior; Breathing; COVID-19; COVID-19 pandemic; Child; Clinical; Data; Development; Disease; Dose; Environment; Epidemic; Exposure to; Female; Financial compensation; Foundations; Goals; Healthcare; Impairment; Incidence; Infant; Infant Mortality; Infection; Inflammation; Inflammatory; Influenza; Investigation; Ketoprofen; Knowledge; Lead; Left; Life; Lipopolysaccharides; Long-Term Effects; Mediating; Microglia; Minority Graduate Student; Modeling; Motor; Neonatal; Newborn Infant; Outcome; Parents; Pathway interactions; Pharmaceutical Preparations; Plethysmography; Pneumonia; Population; Rattus; Research Training; Resistance; Respiratory System; Sex Differences; Specificity; Stimulus; Structure of phrenic nerve; Symptoms; System; Testing; Time; Underrepresented Minority; United States National Center for Health Statistics; Viral; Virus Diseases; Work; base; critical developmental period; disorder control; experimental study; inflammatory marker; male; neuroinflammation; new therapeutic target; novel; parent grant; relating to nervous system; respiratory; sex; stressor; systemic inflammatory response; transcriptomics; treatment strategy

PROJECT SUMMARY/ABSTRACT Viral-induced infections and the corresponding inflammation in newborns are common clinical problems, and with continued improvements in health care, more infants (including those born preterm) are surviving. Yet, the long-term impacts on adults of such early life stressors remains poorly understood. Our parent grant is pioneering investigations on the significant and lasting impairments to the respiratory system after neonatal bacterial- induced inflammation. Our work to date shows impairments to multiple pathways of adult respiratory motor plasticity in males and females, even in pathways thought to be inflammation resistant. Preliminary data are identifying sex-specific mechanisms mediating lasting adult neuroinflammation impairments in respiratory control. While this work is critical for understanding lasting impacts of early bacterial inflammation, there is an urgent need to study the growing population of infants exposed to neonatal viral-induced inflammation. This proposal utilizes our robust and well-established experimental foundation from our current award, and the known effects of acute viral-induced inflammation in adults, to test the hypothesis that viral-induced neonatal inflammation significantly impairs adult respiratory motor plasticity. Experimental approaches to complete this study (phrenic nerve recordings in anesthetized rats and plethysmography in unanesthetized rats) are currently being used to test parallel hypotheses with bacterial-induced inflammatory stimuli in the parent grant. Further, we previously demonstrated that acute, adult viral inflammation abolishes adult respiratory motor plasticity in a unique time course involving a different set of inflammatory markers than those observed in bacterial-based inflammation. However, we know little about the effects of neonatal viral inflammation on any aspect of respiratory control. This proposal will be the first to begin characterizing the impact of the COVID-19 pandemic on an understudied and growing population of infants exposed to viral inflammation and the long-term impact of this early life stressor. Results from the proposed studies will significantly advance our understanding of the long-term effects of neonatal viral-induced impairments persisting into adulthood in both sexes. Collectively, the results from the parent grant and this proposal will assess the stimulus specificity of neonatal inflammation (bacterial and viral) on adult respiratory control. The findings from these critical areas of study are necessary to identify adult vulnerability to subsequent inflammatory challenges, identify new therapeutic targets, and establish foundational knowledge to develop novel treatment strategies for adults with ventilatory control disorders.

项目摘要/摘要 病毒引起的感染和新生儿的相应炎症是常见的临床问题，并且 随着医疗保健的持续改善，更多的婴儿（包括出生的早产）正在幸存。但是， 对这种早期生活压力源的成年人的长期影响仍然很少理解。我们的父母赠款是开创性的 对新生儿细菌 - 诱发炎症。迄今 男性和女性的可塑性，即使在被认为具有抗炎的途径中也是如此。初步数据是 确定介导持续的成人神经炎症障碍的性别特异性机制 控制。尽管这项工作对于理解早期细菌炎症的持久影响至关重要，但有一个 迫切需要研究暴露于新生儿病毒引起的炎症的婴儿人群的增长。这 提案利用我们目前奖项中的强大且公认的实验基础，以及已知的 急性病毒引起的成人炎症的作用，以检验病毒诱导的新生儿的假设 炎症严重损害了成人呼吸运动可塑性。实验方法完成 这项研究（麻醉大鼠的神经记录和一体式大鼠中的杂质）是 目前用于测试父母赠款中用细菌诱导的炎症刺激的平行假设。 此外，我们以前证明了急性成人病毒炎症会消除成人呼吸运动 在独特的时间过程中的可塑性涉及与在 基于细菌的炎症。但是，我们对新生儿病毒炎症的影响一无所知 呼吸控制方面。该提案将是第一个开始表征Covid-19的影响的提案 暴露于病毒炎症的婴儿人群中的大流行，长期 这种早期生活压力的影响。拟议研究的结果将大大提高我们的理解 在两性中，新生儿病毒引起的损害的长期影响持续到成年。 总体而言，父母赠款和该提案的结果将评估新生儿的刺激特异性 成人呼吸控制的炎症（细菌和病毒）。这些关键研究领域的发现是 确定成人脆弱性的必要条件，确定新的治疗靶标， 并建立基础知识，以制定通气控制的成年人的新型治疗策略 疾病。