Antioxidative Microelectrodes to Improve Neural Recording Performance

通过皮层内微电极从人类患者的神经元记录的电信号， 已经被用来与计算机通信，控制机器人肢体，最近在VA的一项研究中， 信号质量和有用信号可以被记录的时间长度是 前后矛盾社会的共识是神经组织的炎症反应 至少部分地损害了电极的可靠性。几项研究 已经证明了神经炎症和微电极性能之间的联系。 当炎症细胞识别外来生物制剂（即受损/浸润）时，炎症开始 蛋白质和细胞）。血清蛋白和血细胞侵入中枢神经系统， 微电极植入加重神经炎症反应。细胞和组织是 因为植入微电极而受损在微电极表面， 促炎分子的释放导致神经元变性，并增加 血脑屏障，自我延续的过程。 我们正在探索几种抗氧化方法来提高微电极的可靠性。我们 初步数据表明抗氧化方法是一种非常有前途的策略。具体来说，我们有 使用各种抗氧化剂治疗来证明皮质内微电极的减少， 介导的氧化应激和保护神经元活力。我们最新的改善皮质内 记录可靠性是我们的仿生抗氧化涂层。到目前为止，我们在以下方面取得了进展： 在一种电极类型上进行急性记录。长期录音性能和翻译成其他 电极类型优先。我们的涂层是作为一种平台技术开发的， 任何皮质内微电极基底都具有对附着化学的简单修改。我们 最初的努力集中在平面硅衬底上，以便于表征，成本，以及它们的最新进展。 在文学中的知名度。初步结果表明，我们的抗氧化涂层微电极 减少初始炎症反应，保护电极附近的神经元群， 改善初始记录质量。然而，我们还没有证明涂层可以应用于 其他流行的微电极类型，如临床使用的微电极。我们还需要描述 我们的涂层对神经炎症和记录可靠性的长期影响 性能本方案的创新之处在于应用了一种平台技术， 最大限度地减少皮质内微电极失效的两个主要原因：材料损坏和 生物损伤。这项研究旨在回答临床相关问题，并有可能 通过完成拟定研究直接影响正在进行的和未来的临床试验。

Electrical signals recorded from the neurons of human patients by intracortical microelectrodes have been used to communicate with computers, control robotic limbs, and recently in a VA study, control the patient's own arm. The signal quality and the length of time that useful signals can be recorded are inconsistent. The consensus view of the community is that the inflammatory response of neural tissue that surrounds the microelectrodes, at least in part, compromises electrode reliability. Several studies have demonstrated the connection between neuroinflammation and microelectrode performance. Inflammation is initiated when inflammatory cells recognize foreign biologics (i.e. damaged/infiltrating proteins and cells). Serum proteins and blood-derived cells invade the central nervous system following microelectrode implantation and aggravate the neuroinflammatory response. Cells and tissue are damaged from the trauma of microelectrode implantation. At the microelectrode surface, accumulation of pro-inflammatory molecules causes neuronal degeneration and increases the permeability of the blood-brain barrier, self-perpetuating the process. We are exploring several antioxidative approaches to improve microelectrode reliability. Our preliminary data indicates antioxidative approaches as a highly promising strategy. Specifically, we have used a variety of antioxidant treatments to demonstrate a reduction in intracortical microelectrode- mediated oxidative stress and preserve neuron viability. Our newest strategy for improving intracortical recording reliability is our biomimetic antioxidative coating. Thus far, we have shown improvements in acute recording on one electrode type. Chronic recording performance and translation to additional electrode types is a priority. Our coating was developed as a platform technology that could be applied to any intracortical microelectrode substrate with simple modifications to the attachment chemistry. Our initial efforts focused on planar silicon substrates for ease of characterization, cost, and their recent popularity in the literature. Preliminary results suggest that our antioxidative-coated microelectrodes reduce the initial inflammatory response, preserve neuron populations adjacent to the electrodes, and improve initial recording quality. However, we have yet to demonstrate that the coatings can be applied to other popular microelectrode types, such as those used in the clinic. We also still need to characterize the long-term effects of our coatings on both neuroinflammation and the reliability of recording performance. The innovation of this proposal is in the application of a platform technology to effectively minimize two of the leading causes of intracortical microelectrode failure: materials damage and biological damage. This study is designed to answer clinically-relevant questions, and has the potential to directly impact ongoing and future clinical trials by the completion of the proposed study.