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

Abstract

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.

An implantable biohybrid nerve model towards synaptic deep brain stimulation

“…Commercially available deep brain electrodes have up to 8 electrodes that each stimulate a cubic millimeter of neural tissue including thousands of neurons [16] and axons. Miniaturization of the electrodes combined with improved stimulation protocols have increased the specificity to ∼10 neurons [8]; nevertheless, electrode alignment [17], lack of cell specificity [18, 19, 20, 21], and the immune response [22] limit the feasibility of this technology for long term sensory neurorehabilitation.…”

“…[15].Commercially available deep brain electrodes have up to 8 electrodes that each stimulate a cubic millimeter of neural tissue including thousands of neurons [16] and axons. Miniaturization of the electrodes combined with improved stimulation protocols have increased the specificity to ∼10 neurons [8]; nevertheless, electrode alignment [17], lack of cell specificity [18,19,20,21], and the immune response [22] limit the feasibility of this technology for long term sensory neurorehabilitation.Biohybrid approaches, in which living cells integrated with stimulation electrodes are grafted into the tissue, have been proposed to overcome these challenges [23,24,25,26,27,28]. While allogeneic and xenogeneic transplantations of neurons and organoids into adult brains have functionally integrated new neurons into developed neural networks [29,30], neural implants have yet to leverage this for improving biocompatibility, cell specificity and stimulation resolution.…”

Soft Fiber Electronics Based on Semiconducting Polymer

“…Intraspinal microstimulation has been shown to restore some motor function after spinal cord injury. 471 In general, implanting electrodes in the central nervous system triggers inflammation and scarring, shielding the electrodes and affecting stimulation efficacy. Vara et al reported an electrostimulation probe based on PEDOT coating and carbon microfibers, in which electrons delivered by the carbon microfibers were converted into ions in the PEDOT stereostructure, therefore reducing hazardous reactions and increasing the safe charge injection limit.…”

“…This device structure may provide a feasible solution for highly integrated fiber-like stimulators in the future. Intraspinal microstimulation has been shown to restore some motor function after spinal cord injury . In general, implanting electrodes in the central nervous system triggers inflammation and scarring, shielding the electrodes and affecting stimulation efficacy.…”