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
Department of Chronic Diseases, Metabolism and Ageing (CHROMETA), Translational Research Center for Gastrointestinal Disorders (TARGID), KU Leuven, Leuven, Belgium.
Department of Anatomy & Embryology, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, The Netherlands.
Neurogastroenterol Motil. 2020 Sep;32(9):e13889. doi: 10.1111/nmo.13889. Epub 2020 May 31.
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.
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.
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%).
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.
迷走神经(VN)刺激目前被评估为一种治疗免疫介导疾病的新方法。然而,最佳刺激参数很大程度上取决于可能影响其临床转化的迷走神经组成。因此,我们评估了不同物种的颈段和腹段迷走神经之间是否存在形态学差异。
对小鼠、猪和人类的颈段和腹段迷走神经进行主要碱性蛋白和神经丝F染色,以确定有髓和无髓纤维的百分比和大小。
不同物种之间有髓纤维的百分比相当,但颈段迷走神经中的有髓纤维百分比高于腹段迷走神经。小鼠、猪和人类的颈段迷走神经中,有髓纤维分别占54±4%、47±7%和54±7%。有髓纤维由小直径(小鼠:71%,猪:80%,人类:63%)、中直径(小鼠:21%,猪:18%,人类:33%)和大直径纤维(小鼠:7%,猪:2%,人类:4%)组成。腹段迷走神经主要包含无髓纤维(小鼠:93%,猪:90%,人类:94%)。有髓纤维主要由小直径纤维(小鼠:99%,猪:85%,人类:74%)组成,中直径纤维(小鼠:1%,猪:13%,人类:23%)和大直径纤维较少(小鼠:0%,猪:2%人类:3%)。
在所研究的物种中,迷走神经在有髓和无髓纤维方面的组成在很大程度上相似。人类和猪的迷走神经直径相当,纤维组织数量相似,且包含多个束,这意味着猪的迷走神经可能适合优化临床试验的刺激参数。