Quantified Morphology of the Cervical and Subdiaphragmatic Vagus Nerves of Human, Pig, and Rat.

Quantified Morphology of the Cervical and Subdiaphragmatic Vagus Nerves of Human, Pig, and Rat.
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DOI:
10.3389/fnins.2020.601479
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发表时间:
2020
影响因子:
4.3
通讯作者:
Grill WM
Grill WM
中科院分区:
医学2区
文献类型:
--
作者:
Pelot NA;Goldhagen GB;Cariello JE;Musselman ED;Clissold KA;Ezzell JA;Grill WM

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有必要了解迷走神经 (VN) 的形态,以设计和提供有效且选择性的迷走神经刺激 (VNS),因为神经形态会影响纤维对电刺激的反应。具体来说,神经直径(以及电极纤维距离)、束直径、束组织和神经束膜厚度都显着影响神经纤维对通过袖带电极传递的电信号的响应。我们量化了人类、猪和大鼠的颈部和膈下 VN 的形态:有效神经直径、神经束数量、有效神经束直径、神经内膜、神经束膜和神经外膜组织的比例以及神经束膜厚度。人类和猪的 VN 大小相当(颈部约 2 毫米;膈下约 1.6 毫米),而大鼠神经则小十倍。猪神经的神经束比人类神经多十倍,而且神经束更小(颈椎有 47 个神经束,膈下有 7 个神经束;膈下有 38 个神经束,对 5 个神经束)。比较颈部和膈下的 VN,所有物种的颈部神经和神经束都更大,并且猪的神经束更多。与猪和大鼠相比,人类形态在样本之间通常表现出更大的变异性。先前对人类躯体神经的研究表明,神经束膜厚度与神经束直径的比率在整个神经束直径上大致恒定。然而,我们的数据发现人和猪的 VN 神经束膜比之前的数据更厚:对于较大的神经束,VN 具有较厚的神经束膜;对于较小的神经束,VN 具有较厚的神经束膜,按神经束直径归一化。了解临床前模型和临床目标之间 VN 形态的这些差异,以及物种个体之间的变异性,对于设计合适的袖带电极和刺激参数以及将临床前结果转化为临床应用以提高 VNS 的治疗效果至关重要。
It is necessary to understand the morphology of the vagus nerve (VN) to design and deliver effective and selective vagus nerve stimulation (VNS) because nerve morphology influences fiber responses to electrical stimulation. Specifically, nerve diameter (and thus, electrode-fiber distance), fascicle diameter, fascicular organization, and perineurium thickness all significantly affect the responses of nerve fibers to electrical signals delivered through a cuff electrode. We quantified the morphology of cervical and subdiaphragmatic VNs in humans, pigs, and rats: effective nerve diameter, number of fascicles, effective fascicle diameters, proportions of endoneurial, perineurial, and epineurial tissues, and perineurium thickness. The human and pig VNs were comparable sizes (∼2 mm cervically; ∼1.6 mm subdiaphragmatically), while the rat nerves were ten times smaller. The pig nerves had ten times more fascicles—and the fascicles were smaller—than in human nerves (47 vs. 7 fascicles cervically; 38 vs. 5 fascicles subdiaphragmatically). Comparing the cervical to the subdiaphragmatic VNs, the nerves and fascicles were larger at the cervical level for all species and there were more fascicles for pigs. Human morphology generally exhibited greater variability across samples than pigs and rats. A prior study of human somatic nerves indicated that the ratio of perineurium thickness to fascicle diameter was approximately constant across fascicle diameters. However, our data found thicker human and pig VN perineurium than those prior data: the VNs had thicker perineurium for larger fascicles and thicker perineurium normalized by fascicle diameter for smaller fascicles. Understanding these differences in VN morphology between preclinical models and the clinical target, as well as the variability across individuals of a species, is essential for designing suitable cuff electrodes and stimulation parameters and for informing translation of preclinical results to clinical application to advance the therapeutic efficacy of VNS.
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