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 是有限的、可以分析神经疾病严重程度的高通量平台 目前还缺乏具有代表性的体内环境研究。这项建议反映了一项基础性的 我的实验室致力于生成高通量、定量、实时的细胞成像方法和 纳米颗粒在新生儿或围产期大脑中的三维行为 疾病。我们将特别关注神经炎作为常见疾病的标志和 使用自闭症转基因大鼠模型。这种方法将开辟研究的新途径 生命科学和临床科学，通过提供评估以下过程的平台 目前无法获得高通量研究，包括发展过程(即 突触发生)和液体流动的正常调节(即通过 淋巴系统)。此外，跟踪和模拟纳米粒子在或 损伤后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的相互作用来开发治疗技术 疾病特征可以通过以下方式更有效地在疾病之间转换治疗方法 共同的病理生理特征。鉴于炎症是许多人的共同因素 中枢神经系统(CNS)疾病的研究结果有望提供见解和翻译 从本提案中使用的自闭症模型到包括成人在内的其他脑部疾病模型。

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.