# Brain Circulatory Adaptations of Fetal Alcohol Spectrum Disorders

> **NIH NIH F31** · TEXAS A&M AGRILIFE RESEARCH · 2020 · $35,702

## Abstract

Prenatal alcohol exposure (PAE) can give rise to an array of irreversible damages to the developing fetus,
known as fetal alcohol spectrum disorders (FASD). Alcohol's actions during pregnancy are complex and produce
a myriad of heterogeneous outcomes that can affect nearly every fetal organ system. To date, no approved
therapeutic drug exists for FASD, and the prevalence is estimated to be 3-9% in school-age children in the U.S.
 Despite nearly every brain region exhibiting vulnerability to PAE, a substantial knowledge gap persists
regarding how PAE affects vascular function in the developing brain. Circulatory infrastructure develops
concomitantly with the brain, and thus, impairment of brain circulatory function may result in altered nutrient,
oxygen, metabolite, and hormone delivery to the brain during critical developmental windows. Delivery of these
substrates is essential for proper neurodevelopment, and consequently, alcohol-induced disturbances of
substrate delivery to the brain could have a profound effect on neurodevelopmental outcomes.
 In our established FASD rat model, we generated preliminary data utilizing high frequency ultrasonography
in utero which showed that chronic binge PAE impairs middle cerebral artery blood flow and velocity time interval,
a widely utilized indicator of resistance. The preliminary data further showed PAE resulted in impaired middle
cerebral artery (MCA) agonist-induced dose-dependent vasodilation. In Aim 1, we will test if PAE will alter fetal
cranially directed blood flow in our FASD model. To accomplish this aim, we will utilize non-invasive, ultra-high
frequency ultrasonography to obtain color and pulse wave Doppler measurements of fetal heart rate, cardiac
output, blood flow, and indices of vascular resistance in the major artery network that directly supplies blood to
the brain (aorta, internal carotid, and MCA). Aim 2 will test if PAE will compromise the response to perfusion
pressure in brain vasculature in early development. To accomplish this aim, we will cannulate the MCA, a major
resistance artery that directly supplies the brain, and will assess if PAE-alters adaptations to pressure-dependent
vascular responses. Aim 3 will test if PAE induces brain artery dysfunction through impairment of endothelial-
derived vasodilatory pathways (NO, PGI2, EDHF). To accomplish this aim, combinations of endothelial-derived
vasodilator pathways will be blocked pharmacologically and vascular function will be assessed using
arteriography followed by assessment of vasodilatory pathways using RNA-seq, immunoblotting,
spectrophotometric assays, and enzyme activity assays.
 Our proposal explores a new frontier of FASD research by developing the first mechanistic framework for
binge alcohol-induced brain circulatory adaptations and identifying alcohol targets in an in vivo model. The
current proposal's goals align with NIAAA strategic plan for 2017-2021 – Objective 1C, on the need to investigate
the circulatory syste...

## Key facts

- **NIH application ID:** 10016074
- **Project number:** 5F31AA027946-02
- **Recipient organization:** TEXAS A&M AGRILIFE RESEARCH
- **Principal Investigator:** Emilie R Lunde
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $35,702
- **Award type:** 5
- **Project period:** 2019-08-30 → 2022-08-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10016074

## Citation

> US National Institutes of Health, RePORTER application 10016074, Brain Circulatory Adaptations of Fetal Alcohol Spectrum Disorders (5F31AA027946-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10016074. Licensed CC0.

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