Organotopic organization of the porcine mid-cervical vagus nerve.

Organotopic organization of the porcine mid-cervical vagus nerve.
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DOI:
10.3389/fnins.2023.963503
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发表时间:
2023
影响因子:
4.3
通讯作者:
Holder, David
Holder, David
中科院分区:
医学2区
文献类型:
--
作者:
Thompson, Nicole;Ravagli, Enrico;Mastitskaya, Svetlana;Iacoviello, Francesco;Stathopoulou, Thaleia-Rengina;Perkins, Justin;Shearing, Paul R.;Aristovich, Kirill;Holder, David

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尽管体神经的束组织的详细表征,在人类和大型哺乳动物颈部迷走神经明显的束的功能解剖是未知的。迷走神经由于其广泛分布于心脏、喉、肺和腹部内脏,因此是电化学领域中的主要干预目标。然而,经批准的迷走神经刺激(VNS)技术的当前实践是刺激整个神经。这产生了对非靶向效应物的不加选择的刺激和不期望的副作用。选择性神经调节现在是一种可能的空间选择性迷走神经袖带。然而,这需要了解袖带放置水平处的神经束组织,以仅告知所需靶器官或功能的选择性。我们用快速神经电阻抗断层扫描和选择性刺激在几毫秒内成像功能,并发现神经内与三个感兴趣的神经束组相关的一致的空间分离区域,这表明器官学。这是独立验证的结构成像跟踪解剖连接从终末器官与microCT和迷走神经的解剖图的发展。这证实了器官组织。在这里,我们显示,为第一次,在猪颈部迷走神经映射到心脏,肺和喉返功能(N = 4)的局部神经束。这些发现为改善VNS的结局铺平了道路,因为通过靶向选择性刺激已识别的器官特异性含纤维束可以减少不必要的副作用,并且该技术在临床上的扩展超出了目前批准的疾病,以治疗心力衰竭,慢性炎症性疾病等。
Despite detailed characterization of fascicular organization of somatic nerves, the functional anatomy of fascicles evident in human and large mammal cervical vagus nerve is unknown. The vagus nerve is a prime target for intervention in the field of electroceuticals due to its extensive distribution to the heart, larynx, lungs, and abdominal viscera. However, current practice of the approved vagus nerve stimulation (VNS) technique is to stimulate the entire nerve. This produces indiscriminate stimulation of non-targeted effectors and undesired side effects. Selective neuromodulation is now a possibility with a spatially-selective vagal nerve cuff. However, this requires the knowledge of the fascicular organization at the level of cuff placement to inform selectivity of only the desired target organ or function. We imaged function over milliseconds with fast neural electrical impedance tomography and selective stimulation, and found consistent spatially separated regions within the nerve correlating with the three fascicular groups of interest, suggesting organotopy. This was independently verified with structural imaging by tracing anatomical connections from the end organ with microCT and the development of an anatomical map of the vagus nerve. This confirmed organotopic organization. Here we show, for the first time, localized fascicles in the porcine cervical vagus nerve which map to cardiac, pulmonary and recurrent laryngeal function (N = 4). These findings pave the way for improved outcomes in VNS as unwanted side effects could be reduced by targeted selective stimulation of identified organ-specific fiber-containing fascicles and the extension of this technique clinically beyond the currently approved disorders to treat heart failure, chronic inflammatory disorders, and more.
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