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.

项目总结/摘要 植入式神经技术，如微电极阵列，为改善 许多神经变性疾病的症状然而，植入后不久，异物 反应发生，这就是研究人员认为降低稳定性和寿命的这些 装置.已建立的生物标志物，如胶质酸神经胶质蛋白和星形胶质细胞增生和刺激， 然而，由于研究机械失配以评估对装置的响应状态， 大脑中的免疫反应还不是很清楚。星形胶质细胞在神经系统中起着重要的作用， 最近，转录组分析证实了钙通道的活性 反应性星形胶质细胞是许多神经退行性疾病的潜在生物标志物， 论文项目，我将研究星形胶质细胞反应性和设备之间的相关性 功能.初步研究表明，钙通道亚型对不同的钙离子通道有不同的反应。 刺激以诱导反应状态。我将使用组织共培养的方法来诱导三种类型的 炎性星形胶质细胞模型，并表征每个模型对探针材料硬度的反应性， 器械特征以及细胞结构、代谢和病理生理遗传学变化 表情我的目标是阐明神经异物反应的途径， 研究人员是一种潜在的生物标志物，可用于有关植入式 神经科技我概述了迄今为止所做的工作、目前和今后的培训战略， 学术，专业和教育进步，因为它涉及到这个项目，并符合 这是我的职业目标。