Extracellular pH monitoring for use in closed-loop vagus nerve stimulation

摘要

Objective. Vagal nerve stimulation (VNS) has shown potential benefits for obesity treatment; however, current devices lack physiological feedback, which limit their efficacy. Changes in extracellular pH (pH_e) have shown to be correlated with neural activity, but have traditionally been measured with glass microelectrodes, which limit their in vivo applicability. Approach. Iridium oxide has previously been shown to be sensitive to fluctuations in pH and is biocompatible. Iridium oxide microelectrodes were inserted into the subdiaphragmatic vagus nerve of anaesthetised rats. Introduction of the gut hormone cholecystokinin (CCK) or distension of the stomach was used to elicit vagal nerve activity. Main results. Iridium oxide microelectrodes have sufficient pH sensitivity to readily detect changes in pH_e associated with both CCK and gastric distension. Furthermore, a custom-made Matlab script was able to use these changes in pH_e to automatically trigger an implanted VNS device. Significance. This is the first study to show pH_e changes in peripheral nerves in vivo. In addition, the demonstration that iridium oxide microelectrodes are sufficiently pH sensitive as to measure changes in pH_e associated with physiological stimuli means they have the potential to be integrated into closed-loop neurostimulating devices.