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

• Published in: Neurogastroenterology and motility Vol. 32; no. 9; pp. e13889 - n/a
• Main Authors: Stakenborg, Nathalie, Gomez‐Pinilla, Pedro J., Verlinden, Thomas J. M., Wolthuis, Albert M., D’Hoore, Andre, Farré, Ricard, Herijgers, Paul, Matteoli, Gianluca, Boeckxstaens, Guy E.
• Format: Journal Article
• Language: English
• Published: Oxford Wiley Subscription Services, Inc 01-09-2020; John Wiley and Sons Inc
• Subjects: Abdomen; Clinical trials; Fibers; histology; human; mouse; Original; pig; Species; Vagus nerve
• ISSN: 1350-1925; 1365-2982
• DOI: 10.1111/nmo.13889

Background
Vagus nerve (VN) stimulation is currently evaluated as a novel approach to treat immune‐mediated disorders. The optimal stimulation parameters, however, largely depend on the VN composition potentially impacting on its clinical translation. Hence, we evaluated whether morphological differences exist between the cervical and abdominal VNs across different species.
Materials and methods
The cervical and abdominal VNs of mouse, pig, and humans were stained for major basic protein and neurofilament F to identify the percentage and size of myelinated and non‐myelinated fibers.
Results
The percentage of myelinated fibers was comparable between species, but was higher in the cervical VN compared with the abdominal VN. The cervical VN contained 54 ± 4%, 47 ± 7%, and 54 ± 7% myelinated fibers in mouse, pig, and humans, respectively. The myelinated fibers consisted of small‐diameter (mouse: 71%, pig: 80%, and humans: 63%), medium‐diameter (mouse: 21%, pig: 18%, and humans: 33%), and large‐diameter fibers (mouse: 7%, pig: 2%, and humans: 4%). The abdominal VN predominantly contained unmyelinated fibers (mouse: 93%, pig: 90%, and humans: 94%). The myelinated fibers mainly consisted of small‐diameter fibers (mouse: 99%, pig: 85%, and humans: 74%) and fewer medium‐diameter (mouse: 1%, pig: 13%, and humans: 23%) and large‐diameter fibers (mouse: 0%, pig: 2%, and humans: 3%).
Conclusion
The VN composition was largely similar with respect to myelinated and unmyelinated fibers in the species studied. Human and porcine VNs had a comparable diameter and similar amounts of fibrous tissue and contained multiple fascicles, implying that the porcine VN may be suitable to optimize stimulation parameters for clinical trials.
The cervical and abdominal vagus nerve have a similar fiber composition across the studied species. However, the cervical vagus nerve generally possess a higher level of myelination compared to its abdominal counterpart, suggesting that higher stimulation parameters are required to activate the abdominal vagus nerve.