Development and characterization of a chronic implant mouse model for vagus nerve stimulation
- The Feinstein Institutes for Medical Research, United States
- University of Colorado Anschutz Medical Campus, United States
- New York University School of Medicine, United States
Abstract
Vagus nerve stimulation (VNS) suppresses inflammation and autoimmune diseases in preclinical and clinical studies. The underlying molecular, neurological, and anatomical mechanisms have been well characterized using acute electrophysiological stimulation of the vagus. However, there are several unanswered mechanistic questions about the effects of chronic VNS, which require solving numerous technical challenges for a long-term interface with the vagus in mice. Here, we describe a scalable model for long-term VNS in mice developed and validated in 4 research laboratories. We observed significant heart rate responses for at least 4 weeks in 60-90% of animals. Device implantation did not impair vagus-mediated reflexes. VNS using this implant significantly suppressed TNF levels in endotoxemia. Histological examination of implanted nerves revealed fibrotic encapsulation without axonal pathology. This model may be useful to study the physiology of the vagus and provides a tool to systematically investigate long-term VNS as therapy for chronic diseases modeled in mice.
Data availability
All data generated or analyzed during this study are included in the manuscript and supporting files. Source data files have been provided for Figures 2, 3, and 4.
Article and author information
Author details
Ibrahim T Mughrabi
Funding
Defense Advanced Research Projects Agency (HR0011-17-2-0025)
- Stavros Zanos
United Therapeutics Corporation
- Stavros Zanos
Boston Scientific Corporation
- Yousef Al-Abed
Defense Advanced Research Projects Agency (HR0011-17-2-0051)
- Cristin Welle
Defense Advanced Research Projects Agency (N66001-17-2-4010)
- Robert C Froemke
Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD088411)
- Robert C Froemke
Brain Research through Advancing Innovative Neurotechnologies (NS107616)
- Robert C Froemke
National Institute on Deafness and Other Communication Disorders (DC12557)
- Robert C Froemke
Howard Hughes Medical Institute (Faculty Scholarship)
- Robert C Froemke
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All animal experiments complied with relevant ethical guidelines and were approved by the Institutional Animal Care and Use Committee (IACUC) of the Feinstein Institutes for Medical Research (protocol numbers: 2016-029, 2017-010, and 2019-010) and University of Colorado Anschutz Medical Campus (protocol number: 00238).
Reviewing Editor
- Isaac M Chiu, Harvard Medical School, United States
Publication history
- Received: July 20, 2020
- Accepted: April 2, 2021
- Accepted Manuscript published: April 6, 2021 (version 1)
- Version of Record published: April 16, 2021 (version 2)
Copyright
© 2021, Mughrabi et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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