Vagus Nerve Stimulation in Rodent Models: An Overview of Technical Considerations

Abstract

Over the last several decades, vagus nerve stimulation (VNS) has evolved from a treatment for select neuropsychiatric disorders to one that holds promise in treating numerous inflammatory conditions. Growing interest has focused on the use of VNS for other indications, such as heart failure, rheumatoid arthritis, inflammatory bowel disease, ischemic stroke, and traumatic brain injury. As pre-clinical research often guides expansion into new clinical avenues, animal models of VNS have also increased in recent years. To advance this promising treatment, however, there are a number of experimental parameters that must be considered when planning a study, such as physiology of the vagus nerve, electrical stimulation parameters, electrode design, stimulation equipment, and microsurgical technique. In this review, we discuss these important considerations and how a combination of clinically relevant stimulation parameters can be used to achieve beneficial therapeutic results in pre-clinical studies of sub-acute to chronic VNS, and provide a practical guide for performing this work in rodent models. Finally, by integrating clinical and pre-clinical research, we present indeterminate issues as opportunities for future research.

Comparison between the cervical and abdominal vagus nerves in mice, pigs, and humans

“…6,10,37 Yet, the exact mecha- inclusion of recording electrodes); and (e) implantation position. 38,39 In general, C fibers are small, unmyelinated, and thus have a higher excitation threshold than A and B fibers which are larger and myelinated. As the excitation threshold significantly differs depending on the type of vagal fibers targeted, knowledge about the VN composition would be of great interest as it might determine the stimulation parameters to be used in preclinical and clinical studies.…”

“…The VN is typically composed of 3 fiber types including A, B, and C fibers. Their excitation threshold following VNS depends on several factors: (a) fibrous tissue surrounding the nerve fascicles increases resistance, altering the electric field and resulting in increased voltage requirements for fiber excitation; (b) fiber myelination; (c) fiber diameter and (d) the electrode design (eg, cuff vs hook and possible inclusion of recording electrodes); and (e) implantation position 38,39 . In general, C fibers are small, unmyelinated, and thus have a higher excitation threshold than A and B fibers which are larger and myelinated.…”

Probable Mechanism of Antiepileptic Effect of the Vagus Nerve Stimulation in the Context of the Recent Results in Sleep Research

“…Vagus nerve stimulation is widely used as a seizure-preventive action in many types of otherwise incurable epilepsy and is extensively studied for treating other conditions ranging from rheumatoid arthritis to depression (Vonck et al, 2001;Groves and Brown, 2005;Yuan and Silberstein, 2016;Dibue-Adjei et al, 2019;Noller et al, 2019). It is well-known that vagus nerve is engaged in the bidirectional information transfer between the internal organs and the brain, but how changes in activity going along visceral pathways may be related to paroxysmal events occurring in various brain areas remained unclear.…”

Rapid and Low Cost Manufacturing of Cuff Electrodes

“…Although contacts as small as 0.2 mm can be embedded in the cuff, based on our experience with this process, we expect that its principles will be most viable for cuffs with inner diameters of at least 0.5 mm. Thus, future investigators can use this report as a basis for constructing cuff electrodes for smaller nerves, such as the rat vagus nerve whose diameter Pelot et al (2020) report is 0.260 ± 0.025 mm at the cervical level ( Noller et al, 2019 ).…”