Evidence map›Paper›PMID 39546236›Full record

ArticleMethods in molecular biology (Clifton, N.J.)2025

Microglial and Macrophage Plasticity and Regional Cerebral Blood Flow in the Prenatal Brain and Gut Under Vagus Nerve Stimulation.

Colin Wakefield, Marc Courchesne, Karen Nygard, Martin G Frasch

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Article in Methods in molecular biology (Clifton, N.J.), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors.

Colin Wakefield *Drexel School of Medicine, Philadelphia, PA, USA.
Marc Courchesne *Biotron Imaging Facility, Western University, London, ON, Canada.
Karen NygardBiotron Imaging Facility, Western University, London, ON, Canada.
Martin G FraschDepartment of Obstetrics and Gynecology and Institute on Human Development and Disability, University of Washington, Seattle, WA, USA. mfrasch@uw.edu.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

An intricate relationship exists between the vagus nerve and systemic immune cell regulation, specifically during fetal development. Little is known about the connection between the vagus nerve and the brain's regional circulatory control. In this chapter, we present a methodology for studying the impact of vagus nerve signaling on these connections in the developing fetus using the sheep model for human fetal physiology. First, we present the protocol to study the connection between the vagus nerve physiology and the regional cerebral blood flow (rCBF). Next, we detail the protocol for measuring how vagal signaling alters microglial cell plasticity in gut and brain. In previous work, our team showed that vagotomy results in amplified redistribution of rCBF toward subcortical structures in the fetal brain. Conversely, efferent VNS reduces rCBF to cortical structures while afferent VNS diminishes the rise of rCBF to subcortical structures (independent of cortical rCBF) when compared to controls in the fetal brain. Additionally, our team showed that Iba-1 expression, a marker for microglial cellular signaling activation, rises in a dose-dependent relationship with systemic inflammatory activation in the setting of vagotomy. The findings support existing preclinical and clinical evidence in adult human physiology that vagotomy is neuroprotective for neurodegenerative diseases such as Parkinson's likely via a glial cell-mediated mechanism. Vagus nerve stimulation (VNS) has also been shown to alter rCBF patterns in adults with treatment-resistant depression, underscoring the importance of further investigation of the relationship between the vagus nerve and rCBF as early as in utero. Together, the body of evidence emphasizes that the vagal pathway is an important player in the programming of microglial cell phenotypes within the developing brain. Further study is needed to better understand the significance of these relationships for the development and treatment of early susceptibility to neuroinflammatory and neurodegenerative disorders in later life. Therefore, we present a methodology for assessing rCBF and morphometric features of microglial and macrophage cell activation to allow future teams to expand on the existing body of work and further examine these relationships at a cellular and systems' levels.

Indexed as

BrainCerebrovascular CirculationMacrophagesMicrogliaVagus NerveVagus Nerve StimulationAnimalsCell PlasticityFemaleFetusHumansPregnancySheepBrainCerebral blood flowFetal developmentImmune systemVagus nerve

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.