# Delaware INBRE

> **NIH NIH P20** · UNIVERSITY OF DELAWARE · 2024 · $846,312

## Abstract

PROJECT SUMMARY/ABSTRACT
Neonatal hypoxic ischemic encephalopathy (HIE) is the most common cause of cerebral palsy in children born
at term. Affected children are also at significantly increased risk of learning disorders, intellectual disability,
ADHD and Autism and these neurodevelopmental impairments can result in lifelong disability. HIE can be
caused by any condition that impairs blood or oxygen delivery to the fetal brain around the time of birth,
including maternal infection or inflammation, placental insufficiency/abruption, chorioamnionitis, among other
factors. Therapeutic hypothermia is currently the only effective therapy for HIE, however, 40-50% of infants die
or have moderate to severe neurodevelopmental disability despite undergoing this therapy. Furthermore, many
affected infants are not offered this therapy due to the narrow time window to initiate this treatment after birth.
Therefore, it is critical to develop a complete understanding of the mechanisms of injury to develop novel or
augmentative therapeutic agents.
Many infants with neonatal encephalopathy, the clinical indicator of cerebral insult that allows infants to
undergo therapeutic hypothermia, are born to mothers with evidence of systemic inflammation (i.e., maternal
fever, chorioamnionitis, viral infection), or they themselves have signs of inflammation (i.e. fever, elevated
WBC count) at the time of birth. This systemic inflammation is not recapitulated in current rodent models of HIE
that rely solely on hypoxic or ischemic insults. Therefore, we developed a novel mouse model of HIE (dual hit
HIE model) that incorporates maternal immune activation (MIA) with deep hypoxia at term equivalence.
Preliminary data demonstrate reduced motor coordination, time to find escape route (Barnes maze) and
reduced grip strength in adult mice. We propose to leverage this promising novel mouse model of HIE for
further investigation of the mechanisms of maternal immune activation and modulation of neonatal
neuroinflammation. Moreover, the model lends itself well to investigating a variety of questions related to brain-
immune function, necessary to understand how the brain and microglia respond to immune activation, how the
brain communicates with peripheral immune molecules and pathogens, and identify novel approaches that
might allow for the selective immunomodulation of microglia in the brain or periphery that could very easily
apply to a variety of neurological disorders or disease states.

## Key facts

- **NIH application ID:** 11044247
- **Project number:** 3P20GM103446-23S8
- **Recipient organization:** UNIVERSITY OF DELAWARE
- **Principal Investigator:** MELINDA K DUNCAN
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $846,312
- **Award type:** 3
- **Project period:** 2001-09-30 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11044247

## Citation

> US National Institutes of Health, RePORTER application 11044247, Delaware INBRE (3P20GM103446-23S8). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/11044247. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*