The effects of electrical stimulation on glial cell behaviour

Abstract

Neural interface devices interact with the central nervous system (CNS) to substitute for some sort of functional deficit and improve quality of life for persons with disabilities. Design of safe, biocompatible neural interface devices is a fast-emerging field of neuroscience research. Development of invasive implant materials designed to directly interface with brain or spinal cord tissue has focussed on mitigation of glial scar reactivity toward the implant itself, but little exists in the literature that directly documents the effects of electrical stimulation on glial cells. In this review, a survey of studies documenting such effects has been compiled and categorized based on the various types of stimulation paradigms used and their observed effects on glia. A hybrid neuroscience cell biology-engineering perspective is offered to highlight considerations that must be made in both disciplines in the development of a safe implant. To advance knowledge on how electrical stimulation affects glia, we also suggest experiments elucidating electrochemical reactions that may occur as a result of electrical stimulation and how such reactions may affect glia. Designing a biocompatible stimulation paradigm should be a forefront consideration in the development of a device with improved safety and longevity.

Wireless control of nerve growth using bipolar electrodes: a new paradigm in electrostimulation

“…Sufficiently large extracellular potentials can alter a cell's membrane potential or influence the threshold required for firing action potentials, but smaller, physiological scale potentials steer neuron growth cone direction and branching, direct migration of neurons, control neural stem cell fates, control glial cell orientation and behaviour, and influence immune and inflammatory mechanisms. 2,4,47,[52][53][54][55] Furthermore, when an injury has occurred, the existence of new endogenous directional fields suggests that regeneration may be enhanced with the help of external fields that modify scar tissue. Implanted materials used to apply larger potentials always have a foreign body response, inducing inflammation and fast encapsulation, which results in an enhanced impedance.…”

“…However, alternating current (AC) fields can occur naturally (e.g., nerve synapse potentials) and when applied exogenously they impact nerve cell function and axon sprouting. 53 The responsiveness of nerve cells to AC fields has led to clinical electrostimulation protocols using AC fields with zero net charge (balanced polarity and intensity when averaged over the cycle) and oscillation frequencies determined empirically. These conditions attempt to minimize tissue damage through net zero delivered charge.…”