Micromotion derived fluid shear stress mediates peri-electrode gliosis through mechanosensitive ion channels

Abstract

Clinical applications for neural implant technologies are steadily advancing. Yet, despite clinical successes, neuroelectrode-based therapies require invasive neurosurgery and can subject local soft-tissues to micro-motion induced mechanical shear, leading to the development of peri-implant scaring. This reactive glial tissue creates a physical barrier to electrical signal propagation, leading to loss of device function. Although peri-electrode gliosis is a well described contributor to neuroelectrode failure, the mechanistic basis behind the initiation and progression of glial scarring remains poorly understood. Here, we develop an in silico model of electrode-induced shear stress to evaluate the evolution of the peri-electrode fluid-filled void, encompassing a solid and viscoelastic liquid/solid interface. This model was subsequently used to inform an in vitro parallel-plate flow model of micromotion mediated peri-electrode fluid shear stress. Ventral mesencephalic E14 rat embryonic in vitro cultures exposed to physiologically relevant fluid shear exhibited upregulation of gliosis-associated proteins and the overexpression of two mechanosensitive ion channel receptors, PIEZO1 and TRPA1, confirmed in vivo in a neural probe induced rat glial scar model. Finally, it was shown in vitro that chemical inhibition/activation of PIEZO1 could exacerbate or attenuate astrocyte reactivity as induced by fluid shear stress and that this was mitochondrial dependant. Together, our results suggests that mechanosensitive ion channels play a major role in the development of the neuroelectrode micromotion induced glial scar and that the modulation of PIEZO1 and TRPA1 through chemical agonist/antagonist may promote chronic electrode stability in vivo.

Brain–Computer Interfaces with Intracortical Implants for Motor and Communication Functions Compensation: Review of Recent Developments

“…Further advances here will be related to the increase of speed, accuracy, and multi-task BCI control by improving the design of neural implants and their biocompatibility; development of methods for obtaining biosignals and improvement of algorithms for their extraction and decoding [16,[91][92][93][94][95][96][97][98][99][100]; adjustment of the BCI design for home use [88,89]. Also, BCI technologies are developed to restore locomotion [48] and use in pediatrics [101]; visual and auditory bionic prostheses are being designed [102].…”