# Microglial Polarization: Brain Injury or Protection in Response to Intrauterine Infection

> **NIH NIH R21** · OREGON HEALTH & SCIENCE UNIVERSITY · 2024 · $481,250

## Abstract

PROJECT SUMMARY
 Neurodevelopmental impairment remains the most vexing issue facing the clinical management of premature
infants. Intrauterine infection and inflammation are significant causes of preterm birth potentially resulting in
lifelong neurodevelopmental impairment, such as cerebral palsy, sensory and cognitive deficits and behavioral
difficulties. Ureaplasma parvum is a bacterial species that is a common cause of preterm labor induced by
intrauterine infection. Antibiotic treatment (Azithromycin) of intrauterine infection by Ureaplasma has been shown
to delay preterm labor and improve fetal lung and fetal hemodynamic outcomes in non-human primates (NHP),
which are the most clinically relevant animal model in which to study human preterm labor and fetal brain injury.
However, mechanisms of neuroinflammation and perinatal brain injury, and the action of antibiotics on the fetal
brain in relation to intrauterine infection remain poorly understood. Microglial polarization into pro- or anti-
inflammatory phenotypes is a mechanism by which systemic inflammation may cause neuroinflammation in the
developing brain. In the current proposal, we aim to investigate whether intrauterine infection by Ureaplasma
parvum results in perinatal brain microglial polarization, oligodendrocyte maturation arrest and white matter
injury. We will utilize our access to brain samples from a unique Fetal and Postnatal Non-Human Primate (NHP)
Tissue Repository collected from preterm birth studies previously conducted in our cohort of pregnant rhesus
macaques at ONPRC. Our NHP model of intrauterine UP infection represents a valuable opportunity and
clinically relevant model system in which to investigate the mechanisms of perinatal neuroinflammation
associated with infection-induced preterm labor across fetal and early postnatal development. In Aim 1 we will
assess microglial polarization in response to intrauterine infection and inflammation and maternal antibiotic
treatment in the fetal and postnatal preterm brain. Aim 2 will investigate mechanisms of oligodendrocyte
progenitor cell maturation and myelination associated with intrauterine Ureaplasma infection. This proposal
utilizes our team's extensive experience in studying pregnancy physiology and fetal neurodevelopment and uses
novel spatial transcriptomic techniques in our unique NHP model of prematurity. Successful completion of this
study, utilizing available stored NHP fetal and postnatal brain samples, will provide essential data on the
mechanisms of fetal neuroinflammation that will contribute to future preclinical studies of the treatment of preterm
labor and perinatal brain injury.

## Key facts

- **NIH application ID:** 10950139
- **Project number:** 1R21HD115831-01
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Meredith Anne Kelleher
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $481,250
- **Award type:** 1
- **Project period:** 2024-09-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10950139

## Citation

> US National Institutes of Health, RePORTER application 10950139, Microglial Polarization: Brain Injury or Protection in Response to Intrauterine Infection (1R21HD115831-01). Retrieved via AI Analytics 2026-07-21 from https://api.ai-analytics.org/grant/nih/10950139. Licensed CC0.

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