Efficiency and Safety of Microstimulation Via Different Electrode Materials

通过不同电极材料进行微刺激的效率和安全性

• 批准号: 10622204
• 负责人: XINYAN Tracy CUI
• 金额: $ 5.19万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-01 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10622204
• 关键词: Acute; Address; Auditory; Autopsy; Award; BRAIN initiative; Behavior; Biological; Biomedical Engineering; Blood - brain barrier anatomy; Blood Vessels; Brain; Caring; Cells; Cerebrovascular system; Charge; Chronic; Cultured Cells; Devices; Electrodes; Engineering; Extravasation; Funding; Future; Gliosis; Goals; Grant; Health; Histology; Implant; In Vitro; Inflammation; Inflammatory; Label; Laboratories; Link; Medicine; Microelectrodes; Microglia; Morphology; Mus; Neuroglia; Neurons; Parents; Patients; Performance; Pericytes; Physicians; Physiological; Plasma Proteins; Predisposition; Property; Proteins; Research; Research Assistant; Research Personnel; Research Project Grants; Research Support; Research Training; Safety; Science; Scientist; Structure; Technology; Tissue Engineering; Tissues; Training; Universities; Visual; base; bioelectronics; biomaterial compatibility; brain parenchyma; brain tissue; calcium indicator; career; electric impedance; experimental study; implantation; improved; in vivo; interest; microstimulation; neural implant; neural stimulation; neuron loss; parent grant; relating to nervous system; response; restoration; somatosensory; success; two photon microscopy

Summary Our laboratory’s long-term goal is to understand and characterize the effects of microelectrode implantation, recording, and stimulation on brain tissue from a physiological perspective in both neuronal and non-neuronal cells, as well as to improve the biological compatibility, device stability, and performance of neural implants through the use of advanced materials and tissue engineering approaches. The goal of the parent BRAIN initiative R01 project is to understand the charge transfer, electrochemical, and biocompatibility properties of electrodes on the efficacy and safety of microstimulation. Researchers have used Microstimulation to infer functional connections between brain structures or causal links between structure and behavior. Currently, microstimulation therapy is gaining interest for the restoration of visual, auditory, and somatosensory functions in addition to applications in bioelectronic medicine. Current neural stimulation parameters and safety limits were primarily established based on macro electrodes using postmortem histology. They should be revised for microelectrodes using technologies that capture dynamic changes to neural tissue health and function. Another challenge with micro-stimulation is its susceptibility to host tissue responses. Implantation of electrodes causes electrode fouling, progressive neuronal loss, and inflammatory gliosis, leading to decreased stimulation efficacy and increased impedance over long-term implantation. To address these challenges, the specific objectives of this project are to assess the acute efficiency and safety limit of neural stimulation via different electrode materials in vivo (Aim 1), examine the effects of stimulation on electrode materials and cultured cells in vitro (Aim 2), and to characterize the chronic safety and stability of microstimulation in vivo from different electrode materials (Aim 3). Diversity supplement funding is requested to support the research and training of Ms. Anna Kelly, who is a recent graduate of the Bioengineering Department at the University of Pittsburgh. Ms. Kelly will participate in the proposed research as a post-baccalaureate research assistant for at least one year, pending grant approval. Ms. Kelly will conduct research directed toward both acute and chronic mouse studies detailed in the parent award's first and third specific aims. In the acute studies, microelectrodes will be implanted into the cortices of mice expressing genetically encoded calcium indicators and/or genetically labeled microglia expressing a fluorescent protein. Through the use of 2-photon microscopy, the stimulation threshold and efficacy of electrode materials and stimulation parameters will be assessed. After comprehensive training via participating in these experiments, Ms. Kelly will conduct her independent project focusing specifically on the response of the blood-brain barrier and vasculature to microstimulation. In particular, these studies will focus on the potential effect of microstimulation on the leakage of cells and/or plasma and protein from the vasculature and the ensuing response in the brain parenchyma, including potential changes to the morphology and behavior of pericytes and vascular-associated microglia, which have been implicated in BBB leakage in response to inflammation.

概括 我们实验室的长期目标是了解和表征微电极植入的影响， 从身体角度进行记录和刺激神经元和非神经元的刺激 细胞，以及改善生物学兼容性，设备稳定性和神经性能的性能 通过使用高级材料和组织工程方法。父母大脑的目标 主动性R01项目是了解电荷转移，电化学和生物相容性特性 微刺激的效率和安全性电极。研究人员使用微刺激来推断 大脑结构之间的功能连接或结构与行为之间的因果关系。现在， 微刺激疗法引起了恢复视觉，听觉和体感功能的兴趣 除了在生物电子医学中应用。当前的神经刺激参数和安全限制为 应使用后验尸组织学基于宏电极来修订它们，主要基于宏电极建立。 使用捕获动态变化对神经元组织健康和功能的动态变化的技术。其他 微型刺激的挑战是其对宿主组织反应的敏感性。植入电子原因 电极结垢，进行性神经元丧失和炎症性神经病，导致刺激下降 在长期植入中的功效和阻抗增加。为了应对这些挑战，具体 该项目的目标是通过不同 体内电极材料（AIM 1），检查刺激对电极材料和培养细胞的影响 体外（AIM 2），并表征来自不同的体内微刺激的慢性安全性和稳定性 电极材料（AIM 3）。要求多样性补充资金以支持研究和培训 安娜·凯利（Anna Kelly）女士，他是匹兹堡大学生物工程系的最新毕业生。多发性硬化症。 凯利（Kelly 等待赠款批准。凯利女士将进行针对急性和慢性小鼠研究的研究 在父母奖的第一个和第三个特定目标中详细介绍。在急性研究中，将植入微电极 进入表达一般编码的钙指标和/或遗传标记的小胶质细胞的小鼠的皮质中 表达荧光蛋白。通过使用2光子显微镜，刺激阈值和效率 将评估电极材料和刺激参数。经过参与的全面培训 在这些实验中，凯利女士将进行她的独立项目，专门针对 血脑屏障和微刺激的脉管系统。特别是，这些研究将集中于潜力 微刺激对脉管系统中细胞和/或血浆和蛋白质泄漏的影响以及随后的 大脑实质中的反应，包括对周细胞的形态和行为的潜在变化和 血管相关的小胶质细胞，在BBB泄漏中响应于炎症。