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[Preprint]. 2025 Oct 7:2025.10.07.680991. [Version 1] doi: 10.1101/2025.10.07.680991

Mechanical Properties of the Developing Brain in a Model of Fetal Alcohol Spectrum Disorders and Relationships to Perineuronal Net Integrity

L Tyler Williams, Katrina A Milbocker, Eva Smith, Cassandra P Bodner, Diego A Caban-Rivera, Matthew D J McGarry, Elijah E W Van Houten, Anna Y Klintsova, Curtis L Johnson
PMCID: PMC12632570  PMID: 41279790

Abstract

Neuroimaging is a useful tool for examining altered neurodevelopmental trajectories in fetal alcohol spectrum disorders (FASD). FASD affects 1 in 20 infants in the United States with higher prevalence in specific regions across the globe. Advanced neuroimaging methods, such as volumetric morphometry and diffusion-weighted imaging, are critical for determining the effectiveness of interventions that support neurodevelopment in FASD. In this study, we introduce the use of magnetic resonance elastography (MRE), a cutting-edge neuroimaging technique used to measure the mechanical properties of brain tissue, to assess the impact of alcohol exposure and combined exercise and environmental complexity intervention on neurodevelopment in a rat model of FASD. Our results indicate that brain stiffness is reduced in juvenile alcohol-exposed rats which is recovered to baseline by adulthood, and damping ratio increases in all rats with age. Additionally, we quantified cortical perineuronal net (PNN) density which follows similar trends to shear stiffness and damping ratio, suggesting MRE may be an effective method for noninvasively monitoring FASD progression related to extracellular matrix integrity.

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