Evidence map›Paper›PMID 27165310›Full record

ArticleJournal of neuroinflammation2016

Decreased neuroinflammation correlates to higher vagus nerve activity fluctuations in near-term ovine fetuses: a case for the afferent cholinergic anti-inflammatory pathway?

M G Frasch, M Szynkaruk, A P Prout, K Nygard, M Cao, R Veldhuizen, R Hammond, B S Richardson

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of neuroinflammation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed, 1 pooled it
3.5field-weighted citation impact, top 8% of its field
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

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

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

42 citing papers in PubMed, 1 synthesis or guideline pooled it, 60 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Review
  8. Article
  9. Article
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  11. Review
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  15. Microglia and Neurodevelopmental Disorders.Annual review of neuroscience · 2022
    Review
  16. Article
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  18. Article
  19. Electroacupuncture Ameliorates Tibial Fracture-Induced Cognitive Dysfunction by ElevatingEvidence-based complementary and alternative medicine : eCAM · 2022
    Article
  20. Review
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

8 authors at 4 institutions in 1 country.

M G FraschDepartment of Obstetrics and Gynaecology, CHU Ste-Justine Research Centre, Faculty of Medicine, Université de Montréal, Montréal, QC, Canada. mfrasch@uw.edu.
M SzynkarukDepartment of Obstetrics and Gynaecology, Lawson Health Research Institute, University of Western Ontario, London, ON, Canada.
A P ProutDepartment of Obstetrics and Gynaecology, Lawson Health Research Institute, University of Western Ontario, London, ON, Canada.
K NygardMicroscopy Imaging@Biotron, University of Western Ontario, London, ON, Canada.
M CaoDepartment of Obstetrics and Gynaecology, CHU Ste-Justine Research Centre, Faculty of Medicine, Université de Montréal, Montréal, QC, Canada.
R VeldhuizenDepartment of Physiology and Pharmacology, University of Western Ontario, London, ON, Canada.
R HammondDepartment of Pathology, University of Western Ontario, London, ON, Canada.
B S RichardsonDepartment of Obstetrics and Gynaecology, Lawson Health Research Institute, University of Western Ontario, London, ON, Canada.
Western University · CALawson Health Research Institute · CACentre Hospitalier Universitaire Sainte-Justine · CAUniversité de Montréal · CA

Funding

CIHR
6 · The paper itself

Abstract

backgroundNeuroinflammation in utero may contribute to brain injury resulting in life-long neurological disabilities. The pivotal role of the efferent cholinergic anti-inflammatory pathway (CAP) in controlling inflammation, e.g., by inhibiting the HMGB1 release, via the macrophages' α7 nicotinic acetylcholine receptor (α7nAChR) has been described in adults, but its importance in the fetus is unknown. Moreover, it is unknown whether CAP may also exert anti-inflammatory effects on the brain via the anatomically predominant afferent component of the vagus nerve.

methodsWe measured microglial activation in the ovine fetal brain near term 24 h after the umbilical cord occlusions mimicking human labor versus controls (no occlusions) by quantifying HMGB1 nucleus-to-cytosol translocation in the Iba1+ and α7nAChR+ microglia. Based on multiple clinical studies in adults and our own work in fetal autonomic nervous system, we gauged the degree of CAP activity in vivo using heart rate variability measure RMSSD that reflects fluctuations in vagus nerve activity.

resultsRMSSD correlated to corresponding plasma IL-1β levels at R = 0.57 (p = 0.02, n = 17) and to white matter microglia cell counts at R = -0.89 (p = 0.03). The insult increased the HMGB1 translocation in α7nAChR+ microglia in a brain region-dependent manner (p < 0.001). In parallel, RMSSD at 1 h post insult correlated with cytosolic HMGB1 of thalamic microglia (R = -0.94, p = 0.005), and RMSSD at pH nadir correlated with microglial α7nAChR in the white matter (R = 0.83, p = 0.04). Overall, higher RMSSD values correlated with lower HMGB1 translocation and higher α7nAChR intensity per area in a brain region-specific manner.

conclusionsAfferent fetal CAP may translate increased vagal cholinergic signaling into suppression of cerebral inflammation in response to near-term hypoxic acidemia as might occur during labor. Our findings suggest a new control mechanism of fetal neuroinflammation via the vagus nerve, providing novel possibilities for its non-invasive monitoring in utero and for targeted treatment.

Indexed as

alpha7 Nicotinic Acetylcholine ReceptorAnimalsBrainBrain StemCalcium-Binding ProteinsDiagnosis, Computer-AssistedDisease Models, AnimalDNA-Binding ProteinsEncephalitisFemaleFetal HypoxiaFetusGene Expression RegulationHeart RateHMGB1 ProteinInterleukin-1betaAIF1 protein, humanalpha7 Nicotinic Acetylcholine ReceptorCalcium-Binding ProteinsDNA-Binding ProteinsHMGB1 ProteinInterleukin-1betaInterleukin-6Microfilament ProteinsProto-Oncogene Proteins c-fosCHRNA7FetusHMGB1HRVLaborMicrogliaRMSSDVagus

Identifiers

PMID27165310
PMCPMC4894374
OpenAlexW2375711781

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.