Quantitative 3D imaging of in situ nanoparticle movement and cellular behavior during neuroinflammation

神经炎症过程中纳米粒子原位运动和细胞行为的定量 3D 成像

• 批准号: 10392274
• 负责人: Elizabeth A Nance
• 金额: $ 2.85万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-01 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10392274
• 关键词: 3-Dimensional; Adult; Behavior; Biological Assay; Biological Sciences; Brain; Brain Diseases; Cells; Central Nervous System Diseases; Clinical Sciences; Developmental Process; Disease; Environment; Excision; Foundations; Inflammation; Injury; Lead; Methodology; Modeling; Molecular; Movement; Neurologic Process; Process Assessment; Rattus; Regulation; Research; Severity of illness; Slice; Technology; Therapeutic; Three-Dimensional Imaging; Time; Transgenic Organisms; Translating; Translations; autism spectrum disorder; cell behavior; cellular imaging; fluid flow; glymphatic system; human disease; imaging modality; in situ imaging; in vivo; insight; nanoparticle; neonatal brain; nervous system disorder; neuroinflammation; perinatal brain; quantitative imaging; synaptogenesis; therapeutic target; wasting

PROJECT SUMMARY Currently, the means to gather real-time molecular information from the diseased human brain is limited, and high-throughput platforms that can assay neurological disease severity representative of the in vivo environment are still lacking. This proposal reflects a foundational effort in my lab to generate a high throughout, quantitative, real-time method of imaging cell and nanoparticle behavior, in 3-dimensions, within the neonatal or perinatal brain in the presence of disease. We will specifically focus on neuroinflammation as a common disease hallmark and use a transgenic rat model of autism. This approach will open up new avenues of research in the life sciences and clinical sciences, by providing a platform for assessment of processes that are currently inaccessible to high- throughput study, including developmental processes (i.e. synaptogenesis) and normal regulation of fluid flow (i.e. regulation of waste removal via the glymphatic system). In addition, tracking and modelling nanoparticle co- localization in, or interaction with, cells following injury could also provide new potential therapeutic targets. Developing therapeutic technologies by leveraging their in vivo interactions with common disease hallmarks can lead to more efficient translation of therapies across diseases with shared pathophysiological features. Given that inflammation is a common factor across many central nervous system (CNS) diseases, results are expected to provide insights and translate from the autism model used in this proposal to other models, including adult, of brain disease.

项目摘要 目前，从患病的人脑中收集实时分子信息的手段有限，并且 可以分析体内环境的神经系统疾病严重程度的高通量平台 仍然缺乏。该建议反映了我实验室中的基本努力，以产生整个范围，定量， 成像细胞和纳米颗粒行为的实时方法，在新生儿或围产期内3维 在存在疾病的情况下的大脑。我们将特别关注神经炎症作为一种常见疾病标志 并使用自闭症的转基因大鼠模型。这种方法将为生命科学研究的新途径开放 和临床科学，通过为评估目前无法访问的流程的平台提供平台 吞吐量研究，包括发育过程（即突触发生）和流体流动的正常调节 （即，通过胶状系统调节废物清除）。另外，跟踪和建模纳米颗粒共同 损伤后的细胞或与细胞相互作用的定位也可以提供新的潜在治疗靶标。 通过利用其体内相互作用与常见疾病标志来开发治疗技术可以 导致具有具有共同病理生理特征的疾病跨疾病的疗法的更有效翻译。给出 这种炎症是许多中枢神经系统（CNS）疾病的常见因素，结果是结果 提供洞察并从本提案中使用的自闭症模型转化为其他模型，包括成人， 脑部疾病。