Development and characterization of a chronic implant mouse model for vagus nerve stimulation
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 four 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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Apr 06, 2021
- Source ID
- 10.7554/elife.61270
Entities
People
- Adam Abbas
- Cristin G Welle
- Dane Thompson
- Eleni S Papadoyannis
- Eric H. Chang
- Ibrahim T. Mughrabi
- Jordan Hickman
- Kevin J. Tracey
- Naveen Jayaprakash
- Robert C Froemke
- Stavros Zanos
- Sunhee C Lee
- Theodoros P. Zanos
- Timir Datta-chaudhuri
- Umair Ahmed
- Yao-Chuan Chang
- Yousef Al-abed
Organizations
- Boston Scientific
- Brain Research Trust
- Defense Advanced Research Projects Agency
- Elmezzi Graduate School
- Eunice Kennedy Shriver National Institute of Child Health and Human Development
- Howard Hughes Medical Institute
- National Institute on Deafness and Other Communication Disorders
- New York University
- The Feinstein Institute for Medical Research
- United Therapeutics
- University of Colorado