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

项目摘要 目前，从患病人脑中收集实时分子信息的手段有限， 可以测定代表体内环境的神经疾病严重程度的高通量平台 仍然缺乏。这个提议反映了我的实验室为产生高通量，定量， 在新生儿或围产期内对细胞和纳米颗粒行为进行三维实时成像的方法 大脑在疾病的存在。我们将特别关注神经炎症作为一种常见疾病的标志 并使用转基因自闭症大鼠模型。这种方法将为生命科学研究开辟新的途径 和临床科学，通过提供一个平台，评估目前尚无法进入的过程， 通量研究，包括发育过程（即突触发生）和液流的正常调节 (i.e.通过胶质淋巴系统调节废物去除）。此外，跟踪和建模纳米粒子共同- 损伤后在细胞中的定位或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疾病标志的体内相互作用来开发治疗技术， 导致在具有共同病理生理学特征的疾病之间更有效地转化治疗。给定 炎症是许多中枢神经系统（CNS）疾病的共同因素， 提供见解，并将本提案中使用的自闭症模型转化为其他模型，包括成人模型， 脑部疾病

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.