Toward a Three-Dimensional Brian Organoid Model to Evaluate Neuro Technology Device

建立三维布莱恩类器官模型来评估神经技术设备

• 批准号: 10558011
• 负责人: Ti'Air Riggins
• 金额: $ 7.62万
• 依托单位: CLEVELAND VA MEDICAL RESEARCH/ED/FDN
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-02-01 至 2022-12-04
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10558011
• 关键词: 3-Dimensional; Actins; Address; Affect; Astrocytes; Atomic Force Microscopy; Basic Science; Biological Assay; Biological Markers; Boron; Brain; Calcium Channel; Cells; Chronic; Clinical Trials; Coculture Techniques; Complement; Complex; Cyclic AMP; Devices; Diamond; Disease; Electrodes; Environment; Female; Foreign Bodies; Future; Gene Expression; Genetic; Genetic Transcription; Glial Fibrillary Acidic Protein; Glutamates; Goals; Hour; Hypertrophy; Immune response; Immune system; Immunochemistry; Implant; Implanted Electrodes; Inflammation; Inflammatory; Injury; Interdisciplinary Study; Ion Channel; Knock-out; Knowledge; Lipopolysaccharides; Literature; Longevity; Measures; Mechanics; Meningeal; Metabolism; Methods; Microelectrodes; Modeling; Molecular; Monitor; Morphology; Motor Cortex; Nerve Degeneration; Neurodegenerative Disorders; Neuronal Plasticity; Neurons; Neurosciences; Noise; Organoids; Pathway interactions; Patients; Performance; Phase; Play; Production; Protein Isoforms; Quadriplegia; Reactive Oxygen Species; Reporting; Research; Research Personnel; Robotics; Role; Self-Help Devices; Signal Transduction; Silicon; Site; Stimulus; Superoxide Dismutase; Surface; Techniques; Technology; Therapeutic Human Experimentation; Time; Tissues; Training; Work; arm; astrogliosis; career; cytokine; design; implantation; improved; knock-down; mechanical device; mechanical properties; migration; neurotechnology; neurotoxic; next generation sequencing; patch clamp; potential biomarker; pre-doctoral; prevent; protein expression; response; skills; targeted treatment; therapeutic target; transcriptome; transcriptome sequencing; wound

Project Summary/Abstract Implantable neurotechnology such as microelectrode arrays offers substantial promise to improve the condition of many neurogenerative diseases. However, shortly after implantation, foreign body response occurs, which is what researchers believe decreases stability and longevity of these devices. Established biomarkers such as glial acid fibrillary protein and astrogliosis and stimuli such as mechanical mismatch are studied to assess the state of response to the devices, however immune response in the brain is not well understood. Astrocytes play an important role in the brain’s immune system and recently, transcriptome analysis has confirmed calcium channel activity of reactive astrocytes to be a potential biomarker in many neurodegenerative diseases, in this dissertation project, I will investigate the correlation between astroglial reactivity and device features. Preliminary studies have demonstrated that calcium channel isoforms respond to different stimuli to induce the reactive state. I will use tissue co-culture methods to induce three types of inflammatory astrocytic models, and characterize each model’s reactivity to probe material stiffness, device features and change in cytoarchitecture, metabolism and pathophysiological genetic expression. I aim to elucidate that pathway in neuro foreign body response, which will give researchers a potential biomarker to target for therapeutic research concerning implantable neurotechnology. I have outlined the work done thus far, current and future training strategies for academic, professional, and educational advancement, as it relates to this project and aligns with this my career goals.

项目摘要/摘要 可植入的神经技术（例如微电极阵列）提供了重大的前途 许多神经发生疾病的状况。但是，植入后不久，异物 发生反应，这是研究人员认为会降低这些的稳定性和寿命 设备。建立的生物标志物，例如神经胶质酸纤维蛋白和星形胶质细胞增多和刺激 由于机械不匹配是研究对设备响应状态的研究，但是 大脑中的免疫反应尚不清楚。星形胶质细胞在 大脑的免疫系统以及最近的转录组分析已经证实了钙通道活性 反应性星形胶质细胞是许多神经退行性疾病中潜在的生物标志物 论文项目，我将研究星形胶质反应性与装置之间的相关性 特征。初步研究表明，钙通道同工型对不同的反应 刺激诱导反应状态。我将使用组织共培养方法诱导三种类型的 炎症星形细胞模型，并表征每个模型对探针材料刚度的反应性， 设备特征和细胞结构，代谢和病理生理通用的变化 表达。我的目的是阐明神经异物反应中的这一途径，这将给予 研究人员的潜在生物标志物针对有关植入的治疗研究的靶向 神经技术。我概述了迄今为止所做的工作，当前和未来的培训策略 学术，专业和教育进步与该项目有关，并与 这是我的职业目标。