SECTION 1: FACTUAL SUMMARY
This pilot study used microcomputed tomography (microCT) and histological validation to examine the thoracic branches of the human vagus nerve, including cardiac, recurrent laryngeal, and pulmonary branches, building on prior evidence of organotopic organization in the pig cervical vagus nerve.
Left and right vagus nerves (n=10) were dissected from human cadavers at the Evelyn Cambridge Surgical Training Centre, preserving cardiac, recurrent laryngeal, and pulmonary branches. Nerves were resected from below the last pulmonary branch to 2 cm cranial to average VNS cuff placement and 5 cm caudal from the nodose ganglion, yielding ~25 cm samples. Sutures marked branching points. Samples were fixed in 10% neutral buffered formalin, iodine-stained, microCT scanned, and subjected to histology and immunohistochemistry (IHC).
Fascicles were segmented and traced in 5 nerves from branching points to cervical level using Vesselucida 360 software on microCT data, despite fascicular (not fiber) resolution. Analyzed features included fascicle trajectory, spatial arrangement at cervical level, longitudinal course and reorganization, fascicle and branch counts, distances between branches and merging/splitting events, and length of discrete fascicle travel before merging.
Histology included Trichrome and H&E staining for nerve diameter, fascicle count/diameter, fiber count/diameter/type. IHC used neurofilament (NF) and myelin basic protein (MBP) antibodies to detect myelinated/non-myelinated fibers via intermediate filaments and myelin sheaths. Neurochemical/microtubule characteristics distinguished fiber types. ChAT immunostaining was not performed due to COVID-19 timeframe constraints and optimization issues on human tissue. Some cross-sections were missing due to practical limits.
Ten nerves were microCT scanned and reconstructed; five proceeded to segmentation. Only three left and two right vagus nerves, fully traced from caudal to cranial, are presented.
Results showed cardiac, pulmonary, and recurrent laryngeal fascicles preserved partial organization near entry points but merged further along the nerve. In left nerves, cardiac and pulmonary fascicles merged while recurrent laryngeal fascicles remained separate. In right nerves, cardiac fascicles merged with both pulmonary and recurrent laryngeal fascicles. Right nerves had larger diameter and more fascicles, with counts varying along length due to anastomoses. The superior cardiac branch remained distinct near the typical vagus nerve stimulation cuff site on both sides.
The study addressed: 1) presence of organotopic organization in human cervical vagus nerve fascicles similar to pig; 2) functional/anatomical differences revealed by histological/IHC markers. It serves as a preliminary tracing and staining study, affected by COVID-19 lab access and timing constraints.
SECTION 2: AT A GLANCE / WHY THIS IS IMPORTANT
At a Glance: This study maps human vagus nerve fascicle organization for cardiac, pulmonary, and laryngeal branches, revealing partial organotopic patterns that merge differently on left vs. right sides, supporting design of selective stimulation cuffs to target cardiac function and avoid off-target effects.
frontiersin.org/journals/neu…