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

基本信息

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
项目类别：
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

项目摘要

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.

项目概要/摘要微电极阵列等可植入神经技术为改善神经功能提供了巨大希望然而，在植入后不久，异物就会出现。发生反应，研究人员认为这会降低这些物质的稳定性和寿命已建立的生物标志物，例如胶质酸纤维蛋白和星形胶质细胞增生以及刺激物。然而，由于研究了机械失配以评估对设备的响应状态星形胶质细胞在大脑中的免疫反应中发挥的重要作用尚不清楚。大脑的免疫系统，最近转录组分析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初步研究表明，钙通道亚型对不同的特征有反应。我将使用组织共培养方法来诱导三种类型的刺激。炎症星形细胞模型，并表征每个模型的反应性以探测材料刚度，装置特征以及细胞结构、代谢和病理生理遗传的变化我的目的是阐明神经异物反应中的这一途径，这将给出研究人员将其作为植入物治疗研究的潜在生物标志物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，因为它与该项目相关并符合这是我的职业目标。