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.

总结 我们实验室的长期目标是了解和表征微电极植入的效果， 记录和刺激脑组织从生理角度在神经元和非神经元 细胞，以及改善神经植入物的生物相容性、装置稳定性和性能 通过使用先进的材料和组织工程方法。父母大脑的目标 R 01项目旨在了解以下物质的电荷转移、电化学和生物相容性 电极对微刺激的有效性和安全性。研究人员利用微刺激来推断 大脑结构之间的功能联系或结构与行为之间的因果联系。目前， 微刺激疗法在恢复视觉、听觉和躯体感觉功能方面越来越受到关注 以及在生物电子医学中的应用。当前神经刺激参数和安全限值 主要基于使用死后组织学的宏观电极建立。应予以修订， 微电极使用捕捉神经组织健康和功能动态变化的技术。另一 微刺激的挑战是其对宿主组织反应的敏感性。电极植入原因 电极污染、进行性神经元丢失和炎性神经胶质增生，导致刺激减少 有效性和增加的阻抗。为了应对这些挑战， 本项目的目的是评估通过不同的神经刺激的急性有效性和安全性限制。 体内电极材料（目的1），检查刺激对电极材料和培养细胞的影响 在体外（目的2），并表征长期的安全性和稳定性的微刺激在体内从不同的 电极材料（目标3）。多样性补充资金被要求支持研究和培训， 女士安娜凯利是匹兹堡大学生物工程系的应届毕业生。女士 凯利将作为学士后研究助理参加这项拟议的研究至少一年， 等待批准凯利女士将进行针对急性和慢性小鼠研究的研究 在家长奖的第一和第三个具体目标详细说明。在急性研究中，将植入微电极 进入表达遗传编码的钙指示剂和/或遗传标记的小胶质细胞的小鼠的皮质 表达荧光蛋白。通过使用双光子显微镜，刺激阈值和功效 将评估电极材料和刺激参数。通过参加培训， 在这些实验中，凯利女士将进行她的独立项目，特别关注的反应， 血脑屏障和脉管系统对微刺激的反应。特别是，这些研究将集中在潜在的 微刺激对细胞和/或血浆和蛋白质从脉管系统渗漏的影响以及随后的 脑实质中的反应，包括周细胞形态和行为的潜在变化， 血管相关的小胶质细胞，其与炎症反应中的BBB渗漏有关。