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

项目总结 目前，从患病的人脑中收集实时分子信息的手段有限，而且 高通量平台，可以分析代表活体环境的神经疾病严重程度 仍然缺乏。这一建议反映了我的实验室的一项基础性努力，即生成高吞吐量、量化的 新生儿或围产期内三维细胞和纳米颗粒行为的实时成像方法 大脑在疾病的存在下。我们将特别关注神经炎作为常见疾病的标志 并使用自闭症转基因大鼠模型。这种方法将开辟生命科学研究的新途径。 和临床科学，通过提供一个平台来评估目前无法访问的高 通过量研究，包括发育过程(即突触发生)和液体流动的正常调节 (即通过流言系统对废物清除进行监管)。此外，对纳米粒子进行跟踪和建模 损伤后细胞内的定位或与细胞的相互作用也可能提供新的潜在治疗靶点。 通过利用体内与常见疾病特征的相互作用来开发治疗技术可以 导致在具有共同病理生理特征的疾病之间更有效地翻译治疗方法。vt.给出 炎症是许多中枢神经系统(CNS)疾病的共同因素，结果令人期待 为了提供见解并将本提案中使用的自闭症模型转换为其他模型，包括成人， 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.