# Neonatal inflammation impairs control of breathing

> **NIH NIH R01** · UNIVERSITY OF OREGON · 2020 · $365,035

## Abstract

PROJECT SUMMARY/ABSTRACT
Bacterial-induced infections and inflammation in newborns are common clinical problems, and with continued
health care improvements, more infants (including those born preterm) are surviving. We have only recently
begun to understand the lasting impact of neonatal inflammation on adult physiology. Specifically,
understanding the impact of neonatal inflammation on adult breathing, a vital homeostatic behavior, is largely
unexplored, and is the focus of this proposal. Based on exciting preliminary data, we hypothesize that
neonatal inflammation significantly impairs the respiratory control network in adulthood. Three specific
hypotheses will be tested to advance our understanding in this developing field: 1) Neonatal inflammation
abolishes multiple known pathways to adult respiratory motor plasticity; 2) Adult subthreshold inflammatory
challenges have stimulus-specific effects on respiratory control following neonatal inflammation; 3) Neonatal
inflammation differentially alters adult microglial and astrocytic inflammatory responses in the spinal cord. An
innovative, multidisciplinary approach will be used to test these hypotheses. Experimental approaches include:
phrenic nerve recordings in anesthetized rats, plethysmography in unanesthetized rats, and transcriptome
profiling in isolated cells from respiratory-related central nervous system (CNS) regions. After bacterial-induced
neonatal inflammation, preliminary data indicate severe deficits in adult respiratory motor plasticity (an
important form of learning and adaptability critical for compensation to lung or neural injury). Interestingly,
acute treatment with anti-inflammatory drugs in adults after neonatal inflammation differentially restores one of
two main pathways to respiratory motor plasticity, suggesting persistent adult inflammation as a consequence
of the neonatal inflammation. Since organisms rarely experience only a single inflammatory challenge in life,
we are testing the vulnerability of the adult respiratory system to subsequent low-level, innocuous inflammatory
challenges. Our preliminary data indicate increased vulnerability of the adult male respiratory control network
(plasticity, chemosensitivity, and mortality) to otherwise innocuous bacterial stimuli after neonatal inflammation,
correlating with increased incidence of adult pathology in males. Since viral infections are common in adults,
we will also investigate the effects of neonatal bacterial inflammation + adult viral inflammation in both sexes.
At a mechanistic level, we find opposing responses to neonatal inflammation in two CNS cell types, astrocytes
and microglia. Astrocytes, which compose the majority of cells in the CNS, show increased inflammatory gene
expression lasting into adulthood, while microglia (CNS resident immune cells) display a blunted or unchanged
gene response. Results from these studies will significantly advance our understanding of neonatal
inflammation-induced impairmen...

## Key facts

- **NIH application ID:** 9935975
- **Project number:** 5R01HL141249-03
- **Recipient organization:** UNIVERSITY OF OREGON
- **Principal Investigator:** Adrianne Genest Huxtable
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $365,035
- **Award type:** 5
- **Project period:** 2018-06-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9935975

## Citation

> US National Institutes of Health, RePORTER application 9935975, Neonatal inflammation impairs control of breathing (5R01HL141249-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9935975. Licensed CC0.

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