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Functional vagotopy in the cervical vagus nerve of the domestic pig: implications for the study of vagus nerve stimulation.

Publication ,  Journal Article
Settell, ML; Pelot, NA; Knudsen, BE; Dingle, AM; McConico, AL; Nicolai, EN; Trevathan, JK; Ezzell, JA; Ross, EK; Gustafson, KJ; Shoffstall, AJ ...
Published in: Journal of neural engineering
April 2020

Given current clinical interest in vagus nerve stimulation (VNS), there are surprisingly few studies characterizing the anatomy of the vagus nerve in large animal models as it pertains to on-and off-target engagement of local fibers. We sought to address this gap by evaluating vagal anatomy in the pig, whose vagus nerve organization and size approximates the human vagus nerve.Here we combined microdissection, histology, and immunohistochemistry to provide data on key features across the cervical vagus nerve in a swine model, and compare our results to other animal models (mouse, rat, dog, non-human primate) and humans.In a swine model we quantified the nerve diameter, number and diameter of fascicles, and distance of fascicles from the epineural surface where stimulating electrodes are placed. We also characterized the relative locations of the superior and recurrent laryngeal branches of the vagus nerve that have been implicated in therapy limiting side effects with common electrode placement. We identified key variants across the cohort that may be important for VNS with respect to changing sympathetic/parasympathetic tone, such as cross-connections to the sympathetic trunk. We discovered that cell bodies of pseudo-unipolar cells aggregate together to form a very distinct grouping within the nodose ganglion. This distinct grouping gives rise to a larger number of smaller fascicles as one moves caudally down the vagus nerve. This often leads to a distinct bimodal organization, or 'vagotopy'. This vagotopy was supported by immunohistochemistry where approximately half of the fascicles were immunoreactive for choline acetyltransferase, and reactive fascicles were generally grouped in one half of the nerve.The vagotopy observed via histology may be advantageous to exploit in design of electrodes/stimulation paradigms. We also placed our data in context of historic and recent histology spanning multiple models, thus providing a comprehensive resource to understand similarities and differences across species.

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Published In

Journal of neural engineering

DOI

EISSN

1741-2552

ISSN

1741-2560

Publication Date

April 2020

Volume

17

Issue

2

Start / End Page

026022

Related Subject Headings

  • Vagus Nerve Stimulation
  • Vagus Nerve
  • Swine
  • Sus scrofa
  • Rats
  • Mice
  • Dogs
  • Biomedical Engineering
  • Animals
  • 4003 Biomedical engineering
 

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Settell, M. L., Pelot, N. A., Knudsen, B. E., Dingle, A. M., McConico, A. L., Nicolai, E. N., … Ludwig, K. A. (2020). Functional vagotopy in the cervical vagus nerve of the domestic pig: implications for the study of vagus nerve stimulation. Journal of Neural Engineering, 17(2), 026022. https://doi.org/10.1088/1741-2552/ab7ad4
Settell, Megan L., Nicole A. Pelot, Bruce E. Knudsen, Aaron M. Dingle, Andrea L. McConico, Evan N. Nicolai, James K. Trevathan, et al. “Functional vagotopy in the cervical vagus nerve of the domestic pig: implications for the study of vagus nerve stimulation.Journal of Neural Engineering 17, no. 2 (April 2020): 026022. https://doi.org/10.1088/1741-2552/ab7ad4.
Settell ML, Pelot NA, Knudsen BE, Dingle AM, McConico AL, Nicolai EN, et al. Functional vagotopy in the cervical vagus nerve of the domestic pig: implications for the study of vagus nerve stimulation. Journal of neural engineering. 2020 Apr;17(2):026022.
Settell, Megan L., et al. “Functional vagotopy in the cervical vagus nerve of the domestic pig: implications for the study of vagus nerve stimulation.Journal of Neural Engineering, vol. 17, no. 2, Apr. 2020, p. 026022. Epmc, doi:10.1088/1741-2552/ab7ad4.
Settell ML, Pelot NA, Knudsen BE, Dingle AM, McConico AL, Nicolai EN, Trevathan JK, Ezzell JA, Ross EK, Gustafson KJ, Shoffstall AJ, Williams JC, Zeng W, Poore SO, Populin LC, Suminski AJ, Grill WM, Ludwig KA. Functional vagotopy in the cervical vagus nerve of the domestic pig: implications for the study of vagus nerve stimulation. Journal of neural engineering. 2020 Apr;17(2):026022.
Journal cover image

Published In

Journal of neural engineering

DOI

EISSN

1741-2552

ISSN

1741-2560

Publication Date

April 2020

Volume

17

Issue

2

Start / End Page

026022

Related Subject Headings

  • Vagus Nerve Stimulation
  • Vagus Nerve
  • Swine
  • Sus scrofa
  • Rats
  • Mice
  • Dogs
  • Biomedical Engineering
  • Animals
  • 4003 Biomedical engineering