# Altered postnatal microglial function following fetal inflammation and its effect on long-term neurodevelopment of neonatal mice

> **NIH NIH K08** · UNIVERSITY OF MINNESOTA · 2021 · $135,702

## Abstract

ABSTRACT: Maternal chorioamnionitis, the most common cause of birth <28 weeks gestation, initiates a
severe, immune reaction in the fetus known as the “Fetal Inflammatory Response Syndrome” (FIRS). A major
consequence for preterm infants with FIRS is a much higher risk of long-term neurodevelopmental disability
compared to preterm infants without FIRS. Brain injury likely occurs due to FIRS-induced prenatal activation of
microglia, the resident immune cell of the central nervous system. Activated microglia contribute to brain injury
for at least two important reasons: 1) Acute prenatal functional changes injure brain cells and divert microglia
from developmental tasks and 2) Altered postnatal function causes abnormal microglial response to postnatal
inflammatory events. The central hypothesis of this proposal is that therapeutic strategies targeting FIRS-
induced mechanisms of prenatal microglial activation or postnatal inflammatory responses will prevent or
resolve microglial functional abnormalities and improve neurodevelopmental outcomes. The aims of the study
are: 1) to elucidate specific FIRS-induced mechanisms of microglial activation utilizing genetic inhibition and
timed ex vivo therapeutic intervention approaches and 2) to test whether inhibition of prenatal microglial
activation or in vivo postnatal microglial responses will normalize microglial function and prevent abnormal
long-term neurodevelopment. The aims will be evaluated by using a murine model of FIRS and postnatal study
of microglial function and long-term neurodevelopmental outcomes. The knowledge gained is anticipated to
lead to the development of therapeutics for preterm infants affected by FIRS and to be broadly applicable to
other neonatal brain injuries, including hypoxic-ischemic encephalopathy and stroke. The research and career
development plans proposed will jointly facilitate the pursuit of the candidate’s long-term goals: 1) to become
an independently-funded laboratory-based investigator in the fields of neonatal neuroimmunology and
neurodevelopment, 2) to translate animal model findings to neonatal clinical studies, 3) to disseminate
research findings nationally/internationally in order to make an impact on neonatal practice, and 4) to be a
faculty mentor to students and trainees at all levels. The long-term goals will be achieved with the aid of
structured mentoring and learning in the laboratory and classroom that will address immediate goals: to
improve research and presentation skills, immunology and neuroscience knowledge, grantsmanship, and
student mentoring. The candidate’s co-mentors were chosen to maximize their strengths related to the
research project and career development plan. Dr. James Lokensgard is a neuroinflammation expert whose
scientific techniques and studies of microglia match with the aims of this proposal. Dr. Michael Georgieff is an
expert in neurodevelopment and preclinical models to assess early life effects on the brain. Collectively, t...

## Key facts

- **NIH application ID:** 10214654
- **Project number:** 5K08HD099246-03
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Tate A. Gisslen
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $135,702
- **Award type:** 5
- **Project period:** 2019-08-09 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10214654

## Citation

> US National Institutes of Health, RePORTER application 10214654, Altered postnatal microglial function following fetal inflammation and its effect on long-term neurodevelopment of neonatal mice (5K08HD099246-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10214654. Licensed CC0.

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