Abstract:
Intracortical microelectrodes (IMEs) are devices designed to be implanted into the cerebral cortex for various neuroscience and neuro-engineering applications. A critical feature of IMEs is their ability to detect neural activity from individual neurons. Currently, IMEs are limited by chronic failure, largely considered to be caused by the prolonged neuroinflammatory response to the implanted devices. Over the past few years, the characterization of the neuroinflammatory response has grown in sophistication, with the most recent advances focusing on mRNA expression following IME implantation. While gene expression studies increase our broad understanding of the relationship between IMEs and cortical tissue, advanced proteomic techniques have not been reported. Proteomic evaluation is necessary to describe the diverse changes in protein expression specific to neuroinflammation, neurodegeneration, or tissue and cellular viability, which could lead to the further development of targeted intervention strategies designed to improve IME functionality. In this study, we have characterized the expression of 62 proteins within 180 μm of the IME implant site at 4-, 8-, and 16-weeks post-implantation. We identified potential targets for immunotherapies, as well as key pathways that contribute to neuronal dieback around the IME implant.
摘要:
皮质内微电极(IME)是旨在植入大脑皮层的设备,用于各种神经科学和神经工程应用。IME的一个关键特征是它们能够从单个神经元检测神经活动。目前,IME受到慢性失败的限制,在很大程度上被认为是由对植入装置的长期神经炎症反应引起的。在过去的几年里,神经炎症反应的特征越来越复杂,最近的进展集中在IME植入后的mRNA表达。虽然基因表达研究增加了我们对IME和皮质组织之间关系的广泛理解,先进的蛋白质组学技术尚未被报道。蛋白质组学评估是必要的,以描述特定于神经炎症的蛋白质表达的不同变化,神经变性,或组织和细胞活力,这可能导致进一步开发旨在改善IME功能的有针对性的干预策略。在这项研究中,我们已经表征了IME植入位点180μm内62种蛋白质在4-,8-,植入后16周。我们确定了免疫疗法的潜在靶点,以及导致IME植入物周围神经元死亡的关键途径。