Department of Medicine, Solna, Karolinska Institutet, Center for Molecular Medicine, Center for Bioelectronic Medicine, Karolinska University Hospital, Stockholm, Solna, Sweden.
J Neural Eng. 2017 Dec;14(6):066005. doi: 10.1088/1741-2552/aa7a42.
Neural reflexes regulate immune responses and homeostasis. Advances in bioelectronic medicine indicate that electrical stimulation of the vagus nerve can be used to treat inflammatory disease, yet the understanding of neural signals that regulate inflammation is incomplete. Current interfaces with the vagus nerve do not permit effective chronic stimulation or recording in mouse models, which is vital to studying the molecular and neurophysiological mechanisms that control inflammation homeostasis in health and disease. We developed an implantable, dual purpose, multi-channel, flexible 'microelectrode' array, for recording and stimulation of the mouse vagus nerve.
The array was microfabricated on an 8 µm layer of highly biocompatible parylene configured with 16 sites. The microelectrode was evaluated by studying the recording and stimulation performance. Mice were chronically implanted with devices for up to 12 weeks.
Using the microelectrode in vivo, high fidelity signals were recorded during physiological challenges (e.g potassium chloride and interleukin-1β), and electrical stimulation of the vagus nerve produced the expected significant reduction of blood levels of tumor necrosis factor (TNF) in endotoxemia. Inflammatory cell infiltration at the microelectrode 12 weeks of implantation was limited according to radial distribution analysis of inflammatory cells.
This novel device provides an important step towards a viable chronic interface for cervical vagus nerve stimulation and recording in mice.
神经反射调节免疫反应和体内平衡。生物电子医学的进步表明,刺激迷走神经可以用于治疗炎症性疾病,但对于调节炎症的神经信号的理解还不完全。目前用于迷走神经的接口无法在小鼠模型中进行有效的慢性刺激或记录,这对于研究控制健康和疾病中炎症平衡的分子和神经生理机制至关重要。我们开发了一种可植入的、双用途的、多通道的、灵活的“微电极”阵列,用于记录和刺激小鼠的迷走神经。
该阵列是在 8 微米厚的高度生物相容的聚对二甲苯层上微加工而成,具有 16 个位点。通过研究记录和刺激性能来评估微电极。将装置慢性植入小鼠体内长达 12 周。
在体内使用微电极,在生理挑战期间(如氯化钾和白细胞介素-1β)记录到了高保真信号,并且刺激迷走神经产生了预期的、显著降低内毒素血症中肿瘤坏死因子(TNF)血液水平的效果。根据对炎症细胞的径向分布分析,在植入 12 周后,微电极处的炎症细胞浸润是有限的。
这种新型装置为在小鼠中实现可行的慢性颈迷走神经刺激和记录提供了重要的一步。