Antioxidative Microelectrodes to Improve Neural Recording Performance

由皮质内微电极记录的人类患者神经元的电信号 被用来与计算机通信，控制机械臂，最近在退伍军人事务部的一项研究中，控制 病人自己的胳膊。信号质量和可记录有用信号的时间长度为 前后不一致。社会各界的共识是，神经组织的炎症反应 这至少在一定程度上影响了微电极的可靠性。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物质(即受损/渗透)时，炎症就开始了 蛋白质和细胞)。血清蛋白和血源性细胞侵袭中枢神经系统 微电极植入并加重神经炎性反应。细胞和组织是 微电极植入创伤造成的损伤。在微电极表面，积累 致炎分子会导致神经元变性并增加血管通透性 血脑屏障，自我延续这一过程。 我们正在探索几种抗氧化方法来提高微电极的可靠性。我们的 初步数据表明，抗氧化方法是一种非常有希望的策略。具体来说，我们有 使用了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存神经元的活性。我们改善皮质内的最新策略 记录可靠性是我们的仿生抗氧化涂层。到目前为止，我们已经在以下方面显示出改进 在一种电极型上进行急性记录。长期录制性能和转换为其他 电极类型是优先考虑的。我们的涂层是作为一种可应用的平台技术开发的 任何皮质内微电极衬底，只需对附着化学进行简单的修改。我们的 最初的努力集中在平面硅衬底上，以便于表征、成本和最近的 在文学作品中很受欢迎。初步结果表明，我们的抗氧化剂涂层微电极 减少最初的炎症反应，保留电极附近的神经元群体，以及 提高初始录制质量。然而，我们还没有证明这种涂层可以应用于 到其他流行的微电极类型，例如临床上使用的那些。我们还需要刻画 我们的涂层对神经炎症和记录可靠性的长期影响 性能。这一方案的创新之处在于应用了一种平台技术来有效地 尽量减少皮质内微电极失效的两个主要原因：材料损坏和 生物破坏。这项研究旨在回答与临床相关的问题，并有可能 通过拟议研究的完成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.