The Faraday Scalpel: Electrochemical Nerve Lesioning Mechanisms Studied in Invertebrate Models

Abstract

Electrical lesioning of nervous tissue is a common surgical intervention and traditionally is carried out using high-amplitude high-frequency currents. These procedures ablate tissue via an irreversible thermocoagulation or electroporation mechanism. In this work, we explore an alternative concept of achieving lesioning using lower-amplitude direct currents (DC). DC is necessarily accompanied by faradaic reactions, which can lead to local chemical changes that affect nervous tissue. We elucidate the electrochemical mechanisms behind DC nerve lesioning using two disparate invertebrate models: the leech (Hirudo verbana) and the locust (Locusta migratoria). These represent convenient low-cost systems for investigating the effects of DC on nerve functionality with simultaneous in situ electrochemical characterization. Using thin film platinum electrodes, we find that discrete electrochemical processes and associated current magnitudes lead to different outcomes. The lowest current density regime leading to lesioning is cathodic < 100 & micro;A/cm(2), corresponding to the oxygen reduction reaction (ORR). ORR leads to oxygen depletion near the electrode surface, thus causing hypoxic lesioning. Using positive and negative control experiments, we confirm this novel cathodic hypoxia lesioning mechanism. By using the conducting polymer PEDOT, which favors ORR with hydrogen peroxide as the product, we find that nerve lesioning proceeds with higher efficiency than with platinum, with hydrogen peroxide toxicity as the primary mechanism leading to lesioning. Higher-level cathodic DC (> 100 & micro;A/cm(2)) corresponds to water electrolysis and leads to more rapid nerve lesioning via local alkalization. Anodic DC also causes rapid nerve lesioning. We find that the current-induced damage apparently is not related to pH changes or water electrolysis, but likely to chloride oxidation and production of reactive chlorine species. Overall, these results reveal critical current densities that can damage nervous tissue via disparate electrochemical mechanisms. These findings lay a foundation for understanding cathodic and anodic DC current effects on neural tissues, informing experimental and device design for lesioning in mammals, and serving as a reference for neural interface safety margins.