Donahue Mary J, Ejneby Malin Silverå, Jakešová Marie, Caravaca April S, Andersson Gabriel, Sahalianov Ihor, Đerek Vedran, Hult Henrik, Olofsson Peder S, Głowacki Eric Daniel
Laboratory of Organic Electronics, Campus Norrköping, Linköping University, SE-60174 Norrköping, Sweden.
Wallenberg Centre for Molecular Medicine, Linköping University, SE-58185 Linköping, Sweden.
J Neural Eng. 2022 Dec 9;19(6). doi: 10.1088/1741-2552/aca1e3.
Vagus nerve stimulation (VNS) is a promising approach for the treatment of a wide variety of debilitating conditions, including autoimmune diseases and intractable epilepsy. Much remains to be learned about the molecular mechanisms involved in vagus nerve regulation of organ function. Despite an abundance of well-characterized rodent models of common chronic diseases, currently available technologies are rarely suitable for the required long-term experiments in freely moving animals, particularly experimental mice. Due to challenging anatomical limitations, many relevant experiments require miniaturized, less invasive, and wireless devices for precise stimulation of the vagus nerve and other peripheral nerves of interest. Our objective is to outline possible solutions to this problem by using nongenetic light-based stimulation.We describe how to design and benchmark new microstimulation devices that are based on transcutaneous photovoltaic stimulation. The approach is to use wired multielectrode cuffs to test different stimulation patterns, and then build photovoltaic stimulators to generate the most optimal patterns. We validate stimulation through heart rate analysis.A range of different stimulation geometries are explored with large differences in performance. Two types of photovoltaic devices are fabricated to deliver stimulation: photocapacitors and photovoltaic flags. The former is simple and more compact, but has limited efficiency. The photovoltaic flag approach is more elaborate, but highly efficient. Both can be used for wireless actuation of the vagus nerve using light impulses.These approaches can enable studies in small animals that were previously challenging, such as long-termstudies for mapping functional vagus nerve innervation. This new knowledge may have potential to support clinical translation of VNS for treatment of select inflammatory and neurologic diseases.
迷走神经刺激（VNS）是一种很有前景的治疗方法，可用于治疗多种使人衰弱的疾病，包括自身免疫性疾病和顽固性癫痫。关于迷走神经对器官功能调节所涉及的分子机制，仍有许多有待了解之处。尽管有大量特征明确的常见慢性疾病的啮齿动物模型，但目前可用的技术很少适用于对自由活动动物，特别是实验小鼠进行所需的长期实验。由于存在具有挑战性的解剖学限制，许多相关实验需要小型化、侵入性较小的无线设备，以精确刺激迷走神经和其他感兴趣的外周神经。我们的目标是通过使用非基因光刺激来概述解决这个问题的可能方案。我们描述了如何设计和评估基于经皮光伏刺激的新型微刺激设备。方法是使用有线多电极袖带测试不同的刺激模式，然后构建光伏刺激器以产生最优化的模式。我们通过心率分析来验证刺激效果。我们探索了一系列不同的刺激几何结构，其性能存在很大差异。制造了两种类型的光伏设备来提供刺激：光电电容器和光伏标记。前者简单且更紧凑，但效率有限。光伏标记方法更精细，但效率很高。两者都可用于利用光脉冲对迷走神经进行无线驱动。这些方法可以使以前具有挑战性的小动物研究成为可能，例如绘制功能性迷走神经支配图谱的长期研究。这些新知识可能有潜力支持VNS治疗某些炎症性和神经性疾病的临床转化。
