Organ- and function-specific anatomical organization of vagal fibers supports fascicular vagus nerve stimulation.
Organ- and function-specific anatomical organization of vagal fibers supports fascicular vagus nerve stimulation.
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DOI：
10.1016/j.brs.2023.02.003
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发表时间：
2023-03
影响因子：
7.7
通讯作者：
Zanos, Stavros
中科院分区：
文献类型：
--
作者：
Jayaprakash, Naveen;Song, Weiguo;Toth, Viktor;Vardhan, Avantika;Levy, Todd;Tomaio, Jacquelyn;Qanud, Khaled;Mughrabi, Ibrahim;Chang, Yao-Chuan;Rob, Moontahinaz;Daytz, Anna;Abbas, Adam;Nassrallah, Zeinab;Volpe, Bruce T.;Tracey, Kevin J.;Al -Abed, Yousef;Datta-Chaudhuri, Timir;Miller, Larry;Barbe, Mary F.;Lee, Sunhee C.;Zanos, Theodoros P.;Zanos, Stavros
迷走神经纤维在束内行进并形成分支来支配器官并调节器官功能。现有的迷走神经刺激（VNS）疗法非选择性地激活迷走神经纤维，通常会导致非目标器官的疗效降低和副作用。迷走神经干内纤维的横向和纵向排列相对于它们介导的功能和它们支配的器官尚不清楚，但这对于选择性迷走神经刺激至关重要。使用微型计算机断层扫描成像，我们跟踪了束状轨迹，发现在猪中，感觉束和运动束在空间上分离于头侧，靠近结状神经节，并合并尾部，朝向下颈椎和上胸部区域；喉部、心脏和肺特异性束在尾部分离并逐渐合并到头部。使用单纤维水平的定量免疫组织化学，我们鉴定和表征了所有迷走神经纤维，发现不同形态类型的纤维在束中分布有差异：有髓传入神经和传出神经占据单独的束，有髓和无髓鞘传出神经也占据单独的束，小的无髓鞘传入神经广泛分布在大多数束中。我们开发了一种多接触袖带电极来适应迷走神经干的束状结构，并用它在麻醉和清醒的猪中提供束选择性颈部 VNS。来自不同纤维类型的复合动作电位以及来自不同器官的生理反应，包括喉肌、咳嗽、呼吸和心率反应，以径向不对称的方式引发，具有与记录的束状组织一致的一致的角度间隔。这些结果表明，迷走神经干中的纤维根据其介导的功能和其支配的器官进行解剖学组织，并且可以被束状颈迷走神经刺激不对称地激活。
Vagal fibers travel inside fascicles and form branches to innervate organs and regulate organ functions. Existing vagus nerve stimulation (VNS) therapies activate vagal fibers non-selectively, often resulting in reduced efficacy and side effects from non-targeted organs. The transverse and longitudinal arrangement of fibers inside the vagal trunk with respect to the functions they mediate and organs they innervate is unknown, however it is crucial for selective VNS. Using micro-computed tomography imaging, we tracked fascicular trajectories and found that, in swine, sensory and motor fascicles are spatially separated cephalad, close to the nodose ganglion, and merge caudad, towards the lower cervical and upper thoracic region; larynx-, heart- and lung-specific fascicles are separated caudad and progressively merge cephalad. Using quantified immunohistochemistry at single fiber level, we identified and characterized all vagal fibers and found that fibers of different morphological types are differentially distributed in fascicles: myelinated afferents and efferents occupy separate fascicles, myelinated and unmyelinated efferents also occupy separate fascicles, and small unmyelinated afferents are widely distributed within most fascicles. We developed a multi-contact cuff electrode to accommodate the fascicular structure of the vagal trunk and used it to deliver fascicle-selective cervical VNS in anesthetized and awake swine. Compound action potentials from distinct fiber types, and physiological responses from different organs, including laryngeal muscle, cough, breathing, and heart rate responses are elicited in a radially asymmetric manner, with consistent angular separations that agree with the documented fascicular organization. These results indicate that fibers in the trunk of the vagus nerve are anatomically organized according to functions they mediate and organs they innervate and can be asymmetrically activated by fascicular cervical VNS.
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