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Updated: Apr 4, 2026

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Use of a Piglet Model for the Study of Anesthetic-induced Developmental Neurotoxicity AIDN: A Translational Neuroscience Approach
Published on: June 11, 2017
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Germ-free piglets display variable neuroinflammatory-like perturbations in prefrontal cortical microglia
Brooke A Lester1, Colin Kelly2, Sara N Henry3
1School of Neuroscience, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061 USA.
Biorxiv : the Preprint Server for Biology
|April 3, 2026
Summary
The absence of gut microbes alters microglia in the developing piglet prefrontal cortex, indicating region-specific immune responses crucial for brain development. This highlights the microbiome
Area of Science:
- Neuroscience
- Immunology
- Developmental Biology
Background:
- Microglia are key immune cells in the brain, essential for neurodevelopment.
- Gut microbiota composition influences brain immune cell function during development.
- Large animal models offer insights into human brain development due to anatomical similarities.
Purpose of the Study:
- To investigate the impact of a germ-free environment on microglial dynamics in the developing porcine brain.
- To assess microglial density and morphology in specific brain regions of piglets lacking a microbiome.
- To explore the molecular signatures of microglial responses in the absence of microbial colonization.
Main Methods:
- Utilized a germ-free porcine model.
- Employed automated software for quantitative analysis of microglial density and morphology.
- Conducted transcriptomic analysis on prefrontal cortex samples.
- Examined three key brain regions: VZ/SVZ, PFCSWM, and PFCII-III.
Main Results:
- No significant differences in microglial density or morphology were observed in the VZ/SVZ or PFCSWM.
- Increased microglial density and activated morphology were found in the PFCII-III of germ-free piglets.
- Transcriptomic data revealed upregulated neuroinflammation-related genes in the PFCII-III.
- These region-specific changes occurred without overall alterations in microglial density.
Conclusions:
- The developing porcine prefrontal cortex exhibits region-specific microglial and immune responses to the absence of microbial colonization.
- Microglia in the prefrontal cortex are sensitive to germ-free conditions, displaying altered morphology and transcriptional profiles.
- Findings underscore the importance of the microbiome in modulating brain immune cell activity during postnatal development, with implications for understanding neurodevelopmental trajectories.

