Electrical stimulation of the dorsal motor nucleus of the vagus in male mice can regulate inflammation without affecting the heart rate.

Autor: Falvey A; Institute of Bioelectronic Medicine, Feinstein Institutes for Medical Research, Northwell Health, 350 Community Drive, Manhasset, NY 11030, USA., Palandira SP; Institute of Bioelectronic Medicine, Feinstein Institutes for Medical Research, Northwell Health, 350 Community Drive, Manhasset, NY 11030, USA; Elmezzi Graduate School of Molecular Medicine, 350 Community Drive, Manhasset, NY 11030, USA., Chavan SS; Institute of Bioelectronic Medicine, Feinstein Institutes for Medical Research, Northwell Health, 350 Community Drive, Manhasset, NY 11030, USA; Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, 500 Hofstra University, Hempstead, NY 11549, USA; Elmezzi Graduate School of Molecular Medicine, 350 Community Drive, Manhasset, NY 11030, USA., Brines M; Institute of Bioelectronic Medicine, Feinstein Institutes for Medical Research, Northwell Health, 350 Community Drive, Manhasset, NY 11030, USA., Dantzer R; University of Texas MD Anderson Cancer Center, Department of Symptom Research, Houston, TX 77030, USA., Tracey KJ; Institute of Bioelectronic Medicine, Feinstein Institutes for Medical Research, Northwell Health, 350 Community Drive, Manhasset, NY 11030, USA; Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, 500 Hofstra University, Hempstead, NY 11549, USA; Elmezzi Graduate School of Molecular Medicine, 350 Community Drive, Manhasset, NY 11030, USA., Pavlov VA; Institute of Bioelectronic Medicine, Feinstein Institutes for Medical Research, Northwell Health, 350 Community Drive, Manhasset, NY 11030, USA; Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, 500 Hofstra University, Hempstead, NY 11549, USA; Elmezzi Graduate School of Molecular Medicine, 350 Community Drive, Manhasset, NY 11030, USA. Electronic address: vpavlov@northwell.edu.
Jazyk: angličtina
Zdroj: Brain, behavior, and immunity [Brain Behav Immun] 2024 Aug; Vol. 120, pp. 630-639. Date of Electronic Publication: 2024 Apr 24.
DOI: 10.1016/j.bbi.2024.04.027
Abstrakt: Background: The vagus nerve plays an important role in neuroimmune interactions and in the regulation of inflammation. A major source of efferent vagus nerve fibers that contribute to the regulation of inflammation is the brainstem dorsal motor nucleus of the vagus (DMN), as recently shown using optogenetics. In contrast to optogenetics, electrical neuromodulation has broad therapeutic implications. However, the anti-inflammatory effectiveness of electrical stimulation of the DMN (eDMNS) and the possible heart rate (HR) alterations associated with this approach have not been investigated. Here, we examined the effects of eDMNS on HR and cytokine levels in mice administered with lipopolysaccharide (LPS, endotoxin) and in mice subjected to cecal ligation and puncture (CLP) sepsis.
Methods: Anesthetized male 8-10-week-old C57BL/6 mice on a stereotaxic frame were subjected to eDMNS using a concentric bipolar electrode inserted into the left or right DMN or sham stimulation. eDMNS (500, 250 or 50 μA at 30 Hz, for 1 min) was performed and HR recorded. In endotoxemia experiments, sham or eDMNS utilizing 250 μA or 50 μA was performed for 5 mins and was followed by LPS (0.5 mg/kg) i.p. administration. eDMNS was also applied in mice with cervical unilateral vagotomy or sham operation. In CLP experiments sham or left eDMNS was performed immediately post CLP. Cytokines and corticosterone were analyzed 90 mins after LPS administration or 24 h after CLP. CLP survival was monitored for 14 days.
Results: Either left or right eDMNS at 500 μA and 250 μA decreased HR, compared with baseline pre-stimulation. This effect was not observed at 50 μA. Left side eDMNS at 50 μA, compared with sham stimulation, significantly decreased serum and splenic levels of the pro-inflammatory cytokine TNF and increased serum levels of the anti-inflammatory cytokine IL-10 during endotoxemia. The anti-inflammatory effect of eDMNS was abrogated in mice with unilateral vagotomy and was not associated with serum corticosterone alterations. Right side eDMNS in endotoxemic mice suppressed serum TNF and increased serum IL-10 levels but had no effects on splenic cytokines. In mice with CLP, left side eDMNS suppressed serum IL-6, as well as splenic IL-6 and increased splenic IL-10 and significantly improved the survival rate of CLP mice.
Conclusions: For the first time we show that a regimen of eDMNS which does not cause bradycardia alleviates LPS-induced inflammation. These eDMNS anti-inflammatory effects require an intact vagus nerve and are not associated with corticosteroid alterations. eDMNS also decreases inflammation and improves survival in a model of polymicrobial sepsis. These findings are of interest for further studies exploring bioelectronic anti-inflammatory approaches targeting the brainstem DMN.
Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [VAP, SSC, and KJT have co-authored patents broadly related to the content of this paper. They have assigned their rights to the Feinstein Institutes for Medical Research. KJT also declares that he is a consultant to SetPoint Medical. RD is a member of the Scientific Advisory Board of GoodCap Pharma, Toronto, Ontario, Canada for work not related to the present study].
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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