A novel flexible cuff-like microelectrode for dual purpose, acute and chronic electrical interfacing with the mouse cervical vagus nerve

Abstract

Objective. Neural reflexes regulate immune response 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. Here, we developed an implantable, dual purpose multi-channel, flexible electrode array, a “microelectrode”, for recording and stimulation of the mouse vagus nerve. Approach. 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. Main Results. Using the microelectrode in vivo, high fidelity signals were recorded during physiological challenges (e.g potassium chloride and interleukin-1 β), 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 implantation at 12 weeks of implantation was limited in our radial distribution analysis of inflammatory cell. Significance. This novel device provides an important step towards a viable chronic interface for cervical vagus nerve stimulation and recording in mice for both acute and chronic applications.

Printable microscale interfaces for long-term peripheral nerve mapping and precision control

“…A number of technical challenges remain. Most neural interfaces -even those composed of flexible thin-films like polyimide (here and ref (Hiebl et al, 2010;Lago et al, 2007;Seo et al, 2016)) and parylene (Caravaca et al, 2017;Chamanzar et al, 2015) -present elastic moduli substantially above the kilopascal-range of the host tissues (Mahan et al, 2015;Novak et al, 2012;Patel et al, 1998), aggravating long-term reactive responses and limiting interface longevity. High-resolution 3D printing offers the possibility of orthogonalizing the mechanical and material properties of an object, such that pliable microscale structures can be created from materials that are otherwise stiff and rigid (Bückmann et al, 2012(Bückmann et al, , 2014.…”

“…Histological inspection showed the nanoclip implant provokes a typical fibrotic response, completely Interestingly, we found limited fibrotic penetration between the nerve and nanoclip up to 11 months after implant (Figure 2c), suggesting the potential for long-term viability of the preparation (Caravaca et al, 2017;Hiebl et al, 2010;Xiang et al, 2016;Xue et al, 2015).…”

Vagus nerve spiking activity associated with locomotion and cortical arousal states in a freely moving rat

“…Recordings of VN signals were performed by wrapping the cervical VN with a cuff‐shaped electrode with the electrode contact sites attached to the inside walls of the cylindrical tube (Figure a). This recording method reduced background noise and increased the signal to noise ratio (Caravaca et al., ; Sahin & Durand, ; Silverman et al., ). The open edge of the cuff‐shaped electrode was connected to an electrical board on an electrode assembly attached to the animal's head (Shikano, Sasaki, et al., ).…”

“…Unveiling spike patterns of the vagus nerve is indispensable to further understand the communication between the brain and visceral organs such as the heart (Hayakawa et al, 2011), digestive organs (Campos et al, 2012;Czaja et al, 2006), and the lung (Han et al, 2018;Weijs et al, 2015). In previous studies, recordings of VN spikes have been performed in anesthetized rodent animals (Caravaca et al, 2017;Harreby et al, 2011;McCallum et al, 2017;Silverman et al, 2018). Here, we developed a new method to record electrical spikes from the cervical VN using a cuff-shaped electrode in a freely moving animal, which was integrated with our existing method to record bioelectrical signals from multiple organs, including the brain, cardiac system, breathing system, and skeletal muscle.…”

“…While early studies performed vagus nerve recordings from anesthetized animals (Caravaca et al., ; Harreby, Sevcencu, & Struijk, ; McCallum et al., ; Silverman et al., ), recordings from freely moving animals have been limited due to technical difficulties. To address this issue, we developed a novel recording method that can monitor vagus nerve (VN) spikes with a cuff‐shaped electrode from a freely moving rat.…”