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

项目摘要 目前，从患病的人脑中收集实时分子信息的方法 是有限的，高通量平台，可以测定神经系统疾病的严重程度， 仍然缺乏体内环境的代表性。该提案反映了一个基本的 在我的实验室努力产生一个高通量，定量，实时成像细胞的方法， 纳米粒子行为，在三维，在新生儿或围产期脑中的存在， 疾病我们将特别关注神经炎症作为一种常见疾病的标志， 使用转基因自闭症大鼠模型。这种方法将开辟新的研究途径， 生命科学和临床科学，为评估 目前无法进行高通量研究，包括发育过程（即， 突触发生）和流体流动的正常调节（即，经由突触发生的废物去除的调节）。 胶质淋巴系统）。此外，跟踪和建模纳米粒子共定位，或 损伤后与细胞的相互作用也可以提供新的潜在治疗靶点。 通过利用它们与常见的生物活性物质的体内相互作用来开发治疗技术 疾病标志可以导致更有效地翻译各种疾病的治疗方法， 共同的病理生理特征。鉴于炎症是许多疾病的共同因素， 中枢神经系统（CNS）疾病，结果预计将提供见解和翻译 从这个建议中使用的自闭症模型到其他模型，包括成人大脑疾病。

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.