Multi-omic spatially resolved analysis of the neuroinflammatory response to intracortical microelectrode arrays

Intracortical microelectrode arrays (MEAs) are devices implanted into the brain's cortex with the ability to record or stimulate neuronal activity. Unfortunately, MEAs tend to fail over chronic time points, limiting their clinical utility. Chronic failure has largely been attributed to the brain's neuroinflammatory response. Until recently, most of what was understood about the neuroinflammatory response to MEAs was learned through immunohistochemical analysis of small numbers of proteins. More recently, gene expression studies have sequenced thousands of mRNA molecules that contribute to neuroinflammation, but few studies have performed large-scale proteomic analyses. To expand the knowledge of molecular mechanisms involved, we have previously investigated the activity of 62 proteins within 180 μm of the MEA implant site using a spatial proteomic platform. In the present study, we are the first to apply large-scale genomics and proteomics to MEAs, as we evaluate changes in both the whole protein-encoding mouse transcriptome and our 62-protein proteomic panel. We further examine the spatial distribution of the neuroinflammatory response within three distinct domains adjacent to the MEA: 0-90 μm, 90-180 μm, and 180-270 μm from the implant site. Our analysis directly compares the gene and protein expression and highlights the need for segmentation based on proximal distance from the implant site. We also identify key pathways associated with immune cell activation, neurodegeneration, and metabolism that likely contribute to MEA failure and could be targeted to improve MEA performance in future studies.