Neonatal inflammation impairs control of breathing

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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.