Neonatal inflammation impairs control of breathing

项目摘要/摘要 病毒引起的感染和相应的炎症是新生儿常见的临床问题， 随着卫生保健的不断改善，更多的婴儿(包括那些早产的婴儿)得以存活。然而， 这种早期生活应激源对成年人的长期影响仍然知之甚少。我们的父母基金是开创性的 新生儿细菌性肺炎后呼吸系统严重、持久损害的研究 引起炎症。到目前为止，我们的工作显示成人呼吸运动的多个通路受损 男性和女性的可塑性，甚至在被认为是抗炎的途径中也是如此。初步数据为 识别成人呼吸系统持久神经炎性损伤的性别特异性机制 控制力。虽然这项工作对于了解早期细菌性炎症的持久影响至关重要，但有一种 迫切需要研究越来越多的婴儿暴露在新生儿病毒引起的炎症中。这 提案利用了我们从当前奖项中获得的强大和成熟的实验基础，以及已知的 成人急性病毒诱导炎症的影响，以检验病毒诱导新生儿炎症的假说 炎症显著损害成人呼吸运动的可塑性。要完成的实验方法 这项研究(麻醉大鼠的膈神经记录和非麻醉大鼠的体积描记)是 目前被用来测试父母拨款中细菌诱导的炎症刺激的平行假说。 此外，我们先前已经证明，急性成人病毒性炎症会导致成人呼吸运动丧失。 涉及一组不同炎症标志物的独特时间过程中的可塑性 细菌引起的炎症。然而，我们对新生儿病毒性炎症对任何 呼吸控制方面。这项提案将是第一个开始描述新冠肺炎影响的提案 对暴露于病毒性炎症和长期感染的未充分研究和不断增长的婴儿人群的大流行 这种早期生活压力源的影响。拟议研究的结果将极大地促进我们对 关于新生儿病毒引起的损伤在男女中持续到成年的长期影响。 总而言之，父母资助的结果和这项提案将评估新生儿刺激的特异性 炎症(细菌和病毒)对成人呼吸控制的影响。这些关键研究领域的发现如下 有必要确定成人对后续炎性挑战的脆弱性，确定新的治疗靶点， 并建立基础知识，为成人呼吸机控制开发新的治疗策略 精神错乱。

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.