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 largest changes in gene expression occurring 24 h post-implantation, and in genes that are involved in multiple innate immune sets including Itgam, Cd14, and Irak4. STATEMENT OF SIGNIFICANCE: Current understanding of the cellular response contributing to the failure of intracortical microelectrodes has been limited to the evaluation of cellular presence around the electrode. Minimal research investigating gene expression profiles of these cells has left a knowledge gap identifying their phenotype. This manuscript represents the first robust investigation of the changes in gene expression levels specific to the innate immune response following intracortical microelectrode implantation. To understand the role of the complement system in response to implanted probes, we performed gene expression profiling over acute time points from implanted subjects and compared them to no-surgery controls. This manuscript provides valuable insights into inflammatory mechanisms at the tissue-probe interface, thus having a high impact on those using intracortical microelectrodes to study and treat neurological diseases and injuries.

Keywords: Brain; Gene expression; Innate immune response; Intracortical microelectrodes; Pattern recognition receptors.