Differential expression of genes involved in the chronic response to intracortical microelectrodes.
Differential expression of genes involved in the chronic response to intracortical microelectrodes.
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DOI：
10.1016/j.actbio.2023.07.038
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发表时间：
2023-07
影响因子：
9.7
通讯作者：
Sydney Song;Lindsey N. Druschel;E. Chan;J. Capadona
中科院分区：
文献类型：
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作者：
Sydney Song;Lindsey N. Druschel;E. Chan;J. Capadona
脑-机接口系统（BMIs）是临床上有价值的设备，可以为脊髓损伤患者提供功能恢复或为需要假体的患者提供更好的整合。皮质内微电极可以以精确控制BMI所需的分辨率记录神经元动作电位。然而，皮质内微电极的记录性能随着时间的推移而逐渐下降，抑制了它们的有用性。性能下降的一个主要原因是对植入微电极的神经炎症反应。神经炎症反应可导致神经变性和植入部位神经胶质瘢痕的形成。历史上，相对较少的已知细胞和蛋白质标记物的组织学成像表征了植入微电极阵列的神经炎症反应。然而，神经炎症需要许多分子参与者来协调反应-这意味着传统方法可能导致不完整的理解。利用工具的最新进展来表征相对或绝对DNA/RNA表达水平，一些小组已经开始探索微电极-组织界面处的基因表达。我们利用NanoString开发的一组自定义的E813神经炎症特异性基因，在微电极-组织界面进行批量组织分析。我们以前的研究特点的急性先天性免疫反应，皮质内微电极。在这里，我们研究了在野生型（WT）小鼠长期植入无功能探针的微电极组织界面的基因表达。我们发现28个差异表达的基因在慢性时间点（4 WK，8 WK和16 WK），许多在补体和细胞外基质系统。此外，表达水平随时间相对稳定。这里确定的基因代表慢性分子球员在微电极植入部位和潜在的治疗目标的长期整合microelectrodeles.Statement的significanceIntracortical微电极可以记录神经元动作电位的精确控制脑机接口系统（BMI）所需的分辨率。然而，皮质内微电极的记录性能随着时间的推移而逐渐下降，抑制了它们的有用性。这些器械下降的一个主要原因是对植入微电极的神经炎症反应。从历史上看，植入微电极阵列的神经炎症的特征是相对较少的已知细胞和蛋白质标记物的组织学成像。很少有研究开始对促进器械介导的神经炎症的分子途径进行更深入的了解。在这里，我们是第一批确定遗传途径的人，这些遗传途径可以代表改善宿主对皮质内微电极的反应并最终改善设备性能的目标。
Brain-Machine Interface systems (BMIs) are clinically valuable devices that can provide functional restoration for patients with spinal cord injury or improved integration for patients requiring prostheses. Intracortical microelectrodes can record neuronal action potentials at a resolution necessary for precisely controlling BMIs. However, intracortical microelectrodes have a demonstrated history of progressive decline in the recording performance with time, inhibiting their usefulness. One major contributor to decreased performance is the neuroinflammatory response to the implanted microelectrodes. The neuroinflammatory response can lead to neurodegeneration and the formation of a glial scar at the implant site. Historically, histological imaging of relatively few known cellular and protein markers has characterized the neuroinflammatory response to implanted microelectrode arrays. However, neuroinflammation requires many molecular players to coordinate the response - meaning traditional methods could result in an incomplete understanding. Taking advantage of recent advancements in tools to characterize the relative or absolute DNA/RNA expression levels, a few groups have begun to explore gene expression at the microelectrode-tissue interface. We have utilized a custom panel of ∼813 neuroinflammatory-specific genes developed with NanoString for bulk tissue analysis at the microelectrode-tissue interface. Our previous studies characterized the acute innate immune response to intracortical microelectrodes. Here we investigated the gene expression at the microelectrode-tissue interface in wild-type (WT) mice chronically implanted with nonfunctioning probes. We found 28 differentially expressed genes at chronic time points (4WK, 8WK, and 16WK), many in the complement and extracellular matrix system. Further, the expression levels were relatively stable over time. Genes identified here represent chronic molecular players at the microelectrode implant sites and potential therapeutic targets for the long-term integration of microelectrodes.Statement of significanceIntracortical microelectrodes can record neuronal action potentials at a resolution necessary for the precise control of Brain-Machine Interface systems (BMIs). However, intracortical microelectrodes have a demonstrated history of progressive declines in the recording performance with time, inhibiting their usefulness. One major contributor to the decline in these devices is the neuroinflammatory response against the implanted microelectrodes. Historically, neuroinflammation to implanted microelectrode arrays has been characterized by histological imaging of relatively few known cellular and protein markers. Few studies have begun to develop a more in-depth understanding of the molecular pathways facilitating device-mediated neuroinflammation. Here, we are among the first to identify genetic pathways that could represent targets to improve the host response to intracortical microelectrodes, and ultimately device performance.