High-resolution 3D demonstration of regional heterogeneity in the glymphatic system

Accumulating evidence indicates that the glymphatic system has a critical role in maintaining brain homeostasis. However, the detailed anatomy of the glymphatic pathway is not well understood, mostly due to a lack of high spatial resolution 3D visualization. In this study, a fluorescence micro-optical sectioning tomography (fMOST) was used to characterize the glymphatic architecture in the mouse brain. At 30 and 120 min after intracisternal infusion with fluorescent dextran (Dex-3), lectin was injected to stain the cerebral vasculature. Using fMOST, a high-resolution 3D dataset of the brain-wide distribution of Dex-3 was acquired. Combined with fluorescence microscopy and microplate array, the heterogeneous glymphatic flow and the preferential irrigated regions were identified. These cerebral regions containing large-caliber penetrating arteries and/or adjacent to the subarachnoid space had more robust CSF flow compared to other regions. Moreover, the major glymphatic vessels for CSF influx and fluid efflux in the entire brain were shown in 3D. This study demonstrates the regional heterogeneity in the glymphatic system and provides an anatomical resource for further investigation of the glymphatic function.

越来越多的证据表明，类淋巴系统在维持大脑内稳态方面起着关键作用。然而，类淋巴通路的详细解剖结构尚未得到很好的理解，这主要是由于缺乏高空间分辨率的三维可视化技术。在这项研究中，使用了荧光显微光学切片断层扫描技术（fMOST）来描绘小鼠大脑中的类淋巴结构。在脑池内注入荧光葡聚糖（Dex - 3）30分钟和120分钟后，注入凝集素对脑血管进行染色。利用fMOST技术，获取了Dex - 3在全脑分布的高分辨率三维数据集。结合荧光显微镜和微孔板阵列，识别出了不均匀的类淋巴流以及优先灌注区域。与其他区域相比，包含大口径穿通动脉和/或靠近蛛网膜下腔的脑区具有更强的脑脊液流动。此外，还以三维形式展示了整个大脑中脑脊液流入和流出的主要类淋巴管。这项研究证明了类淋巴系统的区域异质性，并为进一步研究类淋巴功能提供了解剖学资源。