Department of Biomedical Engineering, Case Western Reserve University, 2071 Martin Luther King Jr. Drive, Cleveland, OH 44106, USA.
Advanced Platform Technology Center, Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, OH 44106, USA.
Cells. 2022 Jul 30;11(15):2348. doi: 10.3390/cells11152348.
Intracortical microelectrodes are a critical component of brain-machine interface (BMI) systems. The recording performance of intracortical microelectrodes used for both basic neuroscience research and clinical applications of BMIs decreases over time, limiting the utility of the devices. The neuroinflammatory response to the microelectrode has been identified as a significant contributing factor to its performance. Traditionally, pathological assessment has been limited to a dozen or so known neuroinflammatory proteins, and only a few groups have begun to explore changes in gene expression following microelectrode implantation. Our initial characterization of gene expression profiles of the neuroinflammatory response to mice implanted with non-functional intracortical probes revealed many upregulated genes that could inform future therapeutic targets. Emphasis was placed on the most significant gene expression changes and genes involved in multiple innate immune sets, including , , , and In previous studies, inhibition of Cluster of Differentiation 14 () improved microelectrode performance for up to two weeks after electrode implantation, suggesting CD14 can be explored as a potential therapeutic target. However, all measures of improvements in signal quality and electrode performance lost statistical significance after two weeks. Therefore, the current study investigated the expression of genes in the neuroinflammatory pathway at the tissue-microelectrode interface in mice to understand better how inhibition was connected to temporary improvements in recording quality over the initial 2-weeks post-surgery, allowing for the identification of potential co-therapeutic targets that may work synergistically with or after CD14 inhibition to improve microelectrode performance.
皮层内微电极是脑机接口 (BMI) 系统的关键组成部分。用于基础神经科学研究和 BMI 临床应用的皮层内微电极的记录性能会随着时间的推移而下降，从而限制了这些设备的实用性。微电极引发的神经炎症反应已被确定为其性能下降的一个重要因素。传统上，病理评估仅限于十几个已知的神经炎症蛋白，只有少数几个研究小组开始探索微电极植入后基因表达的变化。我们最初对植入非功能皮层内探针的小鼠的神经炎症反应的基因表达谱进行了表征，发现了许多上调的基因，这些基因可能为未来的治疗靶点提供信息。研究重点放在了最显著的基因表达变化和涉及多个固有免疫集的基因上，包括 、 、 、 和 。在之前的研究中，抑制分化群 14 (CD14) 可以改善微电极在植入电极后两周内的性能，这表明 CD14 可以作为一个潜在的治疗靶点进行探索。然而，在两周后，所有改善信号质量和电极性能的措施都失去了统计学意义。因此，本研究在 小鼠中研究了神经炎症通路中的基因表达，以更好地了解 CD14 抑制如何与术后最初 2 周内记录质量的暂时改善相关联，从而确定潜在的共同治疗靶点，这些靶点可能与 CD14 抑制协同作用或在其之后发挥作用，以改善微电极性能。
