Differential expression of genes involved in the acute innate immune response to intracortical microelectrodes

Abstract

Higher order tasks in development for brain-computer interfacing applications require the invasiveness of intracortical microelectrodes. Unfortunately, the resulting inflammatory response contributes to the decline of detectable neural signal. The major components of the neuroinflammatory response to microelectrodes have been well-documented with histological imaging, leading to the identification of broad pathways of interest for its inhibition such as oxidative stress and innate immunity. To understand how to mitigate the neuroinflammatory response, a more precise understanding is required. Advancements in genotyping have led the development of new tools for developing temporal gene expression profiles. Therefore, we have meticulously characterized the gene expression profiles of the neuroinflammatory response to mice implanted with non-functional intracortical probes. A time course of differential acute expression of genes of the innate immune response were compared to naïve sham mice, identifying significant changes following implantation. Differential gene expression analysis revealed 22 genes that could inform future therapeutic targets. Particular emphasis is placed on the *

A high-resolution real-time quantification of astrocyte cytokine secretion under shear stress for investigating hydrocephalus shunt failure

“…Along the shunt hole/CSF interface, astrocytes are simultaneously exposed to fluid flow shear stress and TNF-α/IL-1β cytokine stimulation secreted from activated microglia/macrophages on the shunt surface 26 , 27 . Based on reports, shear stress has less effect on microglia/macrophages, but a direct stimulation effect on astrocytes 4 , 5 .…”

Investigating the Association between Motor Function, Neuroinflammation, and Recording Metrics in the Performance of Intracortical Microelectrode Implanted in Motor Cortex

“…BBB disruption has been implicated with affecting the electrode–tissue interface and recording stability [ 37 , 59 ]. Recent studies evaluating the molecular pathways following electrode implantation have further implicated the role BBB disruption has on exposing the brain parenchyma to pro-oxidants, pro-inflammatory factors, and blood-borne molecules [ 21 , 67 , 68 ]. The entrance of such toxins to the brain parenchyma, through BBB disruption, can be linked to neurological damage, as BBB disruption underlies many neurodegenerative neuropathologies [ 69 ].…”

“…Correspondingly, the glial cell response had associations with one another, distinguished by activated microglia/macrophages and reactive astrocytes connections and formed correlative relationships. Glial cells can perpetuate the inflammatory response to implanted electrodes by signaling the presence of damage through the release of pro-inflammatory factors, barricading the electrode by building a glial scar, and damaging the neurons by releasing neurotoxic factors such as reactive oxygen species [ 13 , 15 , 18 , 19 , 20 , 21 , 29 , 43 ]. Expectedly, there is an inverse relationship between the glial cells response and the neuronal density, implying, as there are more glial cells’ activation, there is a decrease in neuronal populations and vice versa.…”

“…The implantation of the IME severs vasculature, thus breaching the blood–brain barrier and initiating the inflammatory response [ 14 , 15 , 16 ]. Local microglia and infiltrating macrophages become activated, releasing cytokines, neurotoxic factors, and reactive oxygen species (ROS) [ 17 , 18 , 19 , 20 , 21 ]. The release of cytokines, neurotoxic factors, and ROS around implanted electrodes results in a perpetual foreign body response, death of neurons, and corrosion and delamination of the microelectrode surface [ 20 , 22 , 23 , 24 , 25 , 26 , 27 , 28 ].…”

Toward Standardization of Electrophysiology and Computational Tissue Strain in Rodent Intracortical Microelectrode Models

“…As can be seen from the aforementioned examples, there are advantages to using both rats and mice when studying IME performance and the evoked tissue response. In fact, our lab has used both interchangeably (Ereifej et al, 2017(Ereifej et al, , 2018Bedell et al, 2018aBedell et al, , 2019Hermann et al, 2018a;Mahajan et al, 2019). The initial intent of this study was to perform an internal check of consistency to ensure that we were justified in using both rodent models.…”