Characterization of plasma cytokine response to intraperitoneally administered LPS & subdiaphragmatic branch vagus nerve stimulation in rat model.

Vagus nerve stimulation (VNS) has been on the forefront of inflammatory disorder research and has yielded many promising results. Questions remain, however, about the biological mechanisms of such treatments and the inconsistencies in the methods used in research efforts. Here, we aimed to clarify t...

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Main Authors: Jesse P Somann, Kelsey M Wasilczuk, Kaitlyn V Neihouser, Jennifer Sturgis, Gabriel O Albors, J Paul Robinson, Terry L Powley, Pedro P Irazoqui
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2019-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0214317
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author Jesse P Somann
Kelsey M Wasilczuk
Kaitlyn V Neihouser
Jennifer Sturgis
Gabriel O Albors
J Paul Robinson
Terry L Powley
Pedro P Irazoqui
author_facet Jesse P Somann
Kelsey M Wasilczuk
Kaitlyn V Neihouser
Jennifer Sturgis
Gabriel O Albors
J Paul Robinson
Terry L Powley
Pedro P Irazoqui
author_sort Jesse P Somann
collection DOAJ
description Vagus nerve stimulation (VNS) has been on the forefront of inflammatory disorder research and has yielded many promising results. Questions remain, however, about the biological mechanisms of such treatments and the inconsistencies in the methods used in research efforts. Here, we aimed to clarify the inflammatory response to intraperitoneal (IP) injections of lipopolysaccharide (LPS) in rats, while analyzing corresponding effects of electrical stimulation to subdiaphragmatic branches (anterior gastric, accessory celiac, and hepatic) of the left vagus nerve. We accomplished an in-depth characterization of the time-varying cytokine cascade response in the serum of 58 rats to an acute IP LPS challenge over a 330-minute period by utilizing curve-fitting and starting point-alignment methods. We then explored the post-LPS neuromodulation effects of electrically stimulating individually cuffed subdiaphragmatic branches. Through our analysis, we found there to be a consistent order of IP LPS cytokine response (IL-10, TNF-α, GM-CSF, IL-17F, IL-6, IL-22, INF-γ). Apart from IL-10, the IP cytokine cascade was more variable in starting time and occurred later than in previously recorded intravenous (IV) challenges. We also found distinct regulatory effects on multiple cytokine levels by each of the three subdiaphragmatic stimulation subsets. While the time-variability of IP LPS use in rats complicates its utility, we have shown it to be a practical, arguably more physiologically relevant method than IV in rats when our methods are used. More importantly, we have shown that selective subdiaphragmatic neurostimulation can be utilized to selectively induce specific effects on inflammation in the body.
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spelling doaj.art-2a5c282edba34dad94b4b947e8e001322022-12-21T22:36:58ZengPublic Library of Science (PLoS)PLoS ONE1932-62032019-01-01143e021431710.1371/journal.pone.0214317Characterization of plasma cytokine response to intraperitoneally administered LPS & subdiaphragmatic branch vagus nerve stimulation in rat model.Jesse P SomannKelsey M WasilczukKaitlyn V NeihouserJennifer SturgisGabriel O AlborsJ Paul RobinsonTerry L PowleyPedro P IrazoquiVagus nerve stimulation (VNS) has been on the forefront of inflammatory disorder research and has yielded many promising results. Questions remain, however, about the biological mechanisms of such treatments and the inconsistencies in the methods used in research efforts. Here, we aimed to clarify the inflammatory response to intraperitoneal (IP) injections of lipopolysaccharide (LPS) in rats, while analyzing corresponding effects of electrical stimulation to subdiaphragmatic branches (anterior gastric, accessory celiac, and hepatic) of the left vagus nerve. We accomplished an in-depth characterization of the time-varying cytokine cascade response in the serum of 58 rats to an acute IP LPS challenge over a 330-minute period by utilizing curve-fitting and starting point-alignment methods. We then explored the post-LPS neuromodulation effects of electrically stimulating individually cuffed subdiaphragmatic branches. Through our analysis, we found there to be a consistent order of IP LPS cytokine response (IL-10, TNF-α, GM-CSF, IL-17F, IL-6, IL-22, INF-γ). Apart from IL-10, the IP cytokine cascade was more variable in starting time and occurred later than in previously recorded intravenous (IV) challenges. We also found distinct regulatory effects on multiple cytokine levels by each of the three subdiaphragmatic stimulation subsets. While the time-variability of IP LPS use in rats complicates its utility, we have shown it to be a practical, arguably more physiologically relevant method than IV in rats when our methods are used. More importantly, we have shown that selective subdiaphragmatic neurostimulation can be utilized to selectively induce specific effects on inflammation in the body.https://doi.org/10.1371/journal.pone.0214317
spellingShingle Jesse P Somann
Kelsey M Wasilczuk
Kaitlyn V Neihouser
Jennifer Sturgis
Gabriel O Albors
J Paul Robinson
Terry L Powley
Pedro P Irazoqui
Characterization of plasma cytokine response to intraperitoneally administered LPS & subdiaphragmatic branch vagus nerve stimulation in rat model.
PLoS ONE
title Characterization of plasma cytokine response to intraperitoneally administered LPS & subdiaphragmatic branch vagus nerve stimulation in rat model.
title_full Characterization of plasma cytokine response to intraperitoneally administered LPS & subdiaphragmatic branch vagus nerve stimulation in rat model.
title_fullStr Characterization of plasma cytokine response to intraperitoneally administered LPS & subdiaphragmatic branch vagus nerve stimulation in rat model.
title_full_unstemmed Characterization of plasma cytokine response to intraperitoneally administered LPS & subdiaphragmatic branch vagus nerve stimulation in rat model.
title_short Characterization of plasma cytokine response to intraperitoneally administered LPS & subdiaphragmatic branch vagus nerve stimulation in rat model.
title_sort characterization of plasma cytokine response to intraperitoneally administered lps subdiaphragmatic branch vagus nerve stimulation in rat model
url https://doi.org/10.1371/journal.pone.0214317
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