# Neural migratory deficits in congenital heart disease

> **NIH NIH R15** · VIRGINIA POLYTECHNIC INST AND ST UNIV · 2020 · $138,644

## Abstract

Project Summary
Congenital heart disease (CHD) is the most common birth defect. Tremendous advances in
surgical strategies and hospital care markedly increased survival rates such that a majority of
CHD infants reach adulthood. CHD survivors often suffer poor neurological outcomes compared
with their peers, which pose substantial burdens on patients and families. The urgent need for
research aimed at identifying the cause(s) of altered brain maturation associated with long-term
neurological deficits in CHD has recently been brought into clinical focus. Reduced cortical
growth is a key signature of altered brain maturation in CHD but the cellular mechanisms
underlying this process remain unknown. The primary goal of our proposal is to determine how
CHD alters neuronal migration to the cortex during critical stages of brain development. To
accomplish this, we will utilize a newly developed preclinical swine model of CHD as a platform
for cell-dynamic studies. With this model, we were previously able to identify key sources of
newborn cortical neurons and disruption to one of their migratory routes. Our novel preliminary
data reveal numerous complex migratory paths of newborn neurons along a diverse host of
substrates during perinatal cortical growth. We propose to test the hypothesis that reduced
cerebral oxygenation in CHD disrupts neural precursor migration to the cortex in a substrate-
dependent manner. Understanding the relationship between newborn neuronal migration along
vulnerable and resistant substrates is a critical step in defining the molecular mechanisms and
micro-environmental cues regulating immature cortical growth in CHD. The proposed
investigation will provide key insights into potential targets for cell-based regenerative strategies
to improve brain maturation and neurological outcomes in the growing CHD population.

## Key facts

- **NIH application ID:** 10162877
- **Project number:** 3R15NS108183-01A1S1
- **Recipient organization:** VIRGINIA POLYTECHNIC INST AND ST UNIV
- **Principal Investigator:** Paul David Morton
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $138,644
- **Award type:** 3
- **Project period:** 2019-04-15 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10162877

## Citation

> US National Institutes of Health, RePORTER application 10162877, Neural migratory deficits in congenital heart disease (3R15NS108183-01A1S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10162877. Licensed CC0.

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