# Dysfunction of the Cerebral Microcirculation by In Utero Exposure to Alcohol

> **NIH NIH R01** · UNIVERSITY OF SOUTH DAKOTA · 2021 · $330,750

## Abstract

Summary/Abstract
Fetal alcohol spectrum disorder (FASD) encompasses a range of developmental disorders that
result from in utero exposure to alcohol. The prevalence of FASD varies widely, but may affect
2-5% of children with an economic burden 9 times that for children without FASD. These
individuals are at a greater risk for cognitive dysfunction, dementia, and seizures. These risks
may be related to impairment in reactivity of cerebral resistance arterioles (small vessel disease
of the brain). However, there is an absence of information regarding cerebrovascular function in
animal models/humans exposed to alcohol in utero. Our central hypothesis is that in utero
exposure to alcohol impairs reactivity of cerebral arterioles, which leads to an increase the
susceptibility of the brain to ischemic damage, and contributes to cognitive/memory/behavior
dysfunction associated with FASD. We propose three specific aims. In Aim #1 we will test the
hypothesis that in utero exposure to alcohol impairs critical vasodilator pathways, but enhances
vasoconstrictor responses, of cerebral arterioles, and thus contributes to small vessel diseases
of the brain. In Aim #2 we will test the hypothesis that in utero exposure to alcohol impairs
responses of cerebral resistance arterioles via pathways that lead to an increase in oxidative
stress. We propose to examine whether inhibition of pathways that contribute to oxidative
stress restores impaired cerebral vascular function and whether this is then related to
cognition/memory/behavior. In Aim #3 we will test the hypothesis that in utero exposure to
alcohol potentiates ischemia-induced brain damage in young and adult rats. We have reported a
relationship between impaired dilation of cerebral arterioles during disease states and brain
damage following cerebral ischemia/reperfusion. Our studies will investigate the novel concept
that in utero exposure to alcohol will negatively impact indices of cerebral vascular function in
young and adult animals, and thus may contribute to cognitive/memory/behavioral abnormalities
observed in children and adults exposed to alcohol in utero. We will utilize state-of-the-art in
vivo techniques to examine functional responses of cerebral arterioles, innovative
molecular/biochemical techniques to examine cellular pathways critical to cerebral vascular
function, and behavioral approaches to identify cognitive/memory/behavior decline to determine
the impact of in utero exposure to alcohol on the brain during development. The information
gained from these studies will lead to a new dogma regarding how in utero exposure to alcohol
contributes to the etiology of cerebral vascular abnormalities in children and adults.

## Key facts

- **NIH application ID:** 10236493
- **Project number:** 5R01AA027206-04
- **Recipient organization:** UNIVERSITY OF SOUTH DAKOTA
- **Principal Investigator:** WILLIAM G MAYHAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $330,750
- **Award type:** 5
- **Project period:** 2018-09-20 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10236493

## Citation

> US National Institutes of Health, RePORTER application 10236493, Dysfunction of the Cerebral Microcirculation by In Utero Exposure to Alcohol (5R01AA027206-04). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10236493. Licensed CC0.

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