Effects of central nervous system electrical stimulation on non-neuronal cells

Over the past few decades, much progress has been made in the clinical use of electrical stimulation of the central nervous system (CNS) to treat an ever-growing number of conditions from Parkinson's disease (PD) to epilepsy as well as for sensory restoration and many other applications. However, little is known about the effects of microstimulation at the cellular level. Most of the existing research focuses on the effects of electrical stimulation on neurons. Other cells of the CNS such as microglia, astrocytes, oligodendrocytes, and vascular endothelial cells have been understudied in terms of their response to stimulation. The varied and critical functions of these cell types are now beginning to be better understood, and their vital roles in brain function in both health and disease are becoming better appreciated. To shed light on the importance of the way electrical stimulation as distinct from device implantation impacts non-neuronal cell types, this review will first summarize common stimulation modalities from the perspective of device design and stimulation parameters and how these different parameters have an impact on the physiological response. Following this, what is known about the responses of different cell types to different stimulation modalities will be summarized, drawing on findings from both clinical studies as well as clinically relevant animal models and in vitro systems.