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Fascicles split or merge every ∼560 microns within the human cervical vagus nerve.

ABSTRACT: Objective.Vagus nerve stimulation (VNS) is Food and Drug Administration-approved for epilepsy, depression, and obesity, and stroke rehabilitation; however, the morphological anatomy of the vagus nerve targeted by stimulatation is poorly understood. Here, we used microCT to quantify the fascicular structure and neuroanatomy of human cervical vagus nerves (cVNs).Approach.We collected eight mid-cVN specimens from five fixed cadavers (three left nerves, five right nerves). Analysis focused on the 'surgical window': 5 cm of length, centered around the VNS implant location. Tissue was stained with osmium tetroxide, embedded in paraffin, and imaged on a microCT scanner. We visualized and quantified the merging and splitting of fascicles, and report a morphometric analysis of fascicles: count, diameter, and area.Main results.In our sample of human cVNs, a fascicle split or merge event was observed every ∼560µm (17.8 ± 6.1 events cm^-1). Mean morphological outcomes included: fascicle count (6.6 ± 2.8 fascicles; range 1-15), fascicle diameter (514 ± 142µm; range 147-1360µm), and total cross-sectional fascicular area (1.32 ± 0.41 mm²; range 0.58-2.27 mm).Significance.The high degree of fascicular splitting and merging, along with wide range in key fascicular morphological parameters across humans may help to explain the clinical heterogeneity in patient responses to VNS. These data will enable modeling and experimental efforts to determine the clinical effect size of such variation. These data will also enable efforts to design improved VNS electrodes.

SUBMITTER: Upadhye AR

PROVIDER: S-EPMC10353574 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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Fascicles split or merge every ∼560 microns within the human cervical vagus nerve.

Upadhye Aniruddha R AR Kolluru Chaitanya C Druschel Lindsey L Al Lababidi Luna L Ahmad Sami S SS Menendez Dhariyat M DM Buyukcelik Ozge N ON Settell Megan L ML Blanz Stephan L SL Jenkins Michael W MW Wilson David L DL Zhang Jing J Tatsuoka Curtis C Grill Warren M WM Pelot Nicole A NA Ludwig Kip A KA Gustafson Kenneth J KJ Shoffstall Andrew J AJ

Journal of neural engineering 20221103 5

<i>Objective.</i>Vagus nerve stimulation (VNS) is Food and Drug Administration-approved for epilepsy, depression, and obesity, and stroke rehabilitation; however, the morphological anatomy of the vagus nerve targeted by stimulatation is poorly understood. Here, we used microCT to quantify the fascicular structure and neuroanatomy of human cervical vagus nerves (cVNs).<i>Approach.</i>We collected eight mid-cVN specimens from five fixed cadavers (three left nerves, five right nerves). Analysis foc ...[more]

PMID: 36174538

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Project description:ObjectiveGiven 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.ApproachHere 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.Main resultsIn 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.SignificanceThe 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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Fascicles split or merge every ∼560 microns within the human cervical vagus nerve.

Publications

Fascicles split or merge every ∼560 microns within the human cervical vagus nerve.

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