Theodor Kocher Institute, University of Bern, Bern, Switzerland.
Institute of Pharmaceutical Sciences, ETH Zürich, Zürich, Switzerland.
EBioMedicine. 2023 May;91:104558. doi: 10.1016/j.ebiom.2023.104558. Epub 2023 Apr 10.
Routes along the olfactory nerves crossing the cribriform plate that extend to lymphatic vessels within the nasal cavity have been identified as a critical cerebrospinal fluid (CSF) outflow pathway. However, it is still unclear how the efflux pathways along the nerves connect to lymphatic vessels or if any functional barriers are present at this site. The aim of this study was to anatomically define the connections between the subarachnoid space and the lymphatic system at the cribriform plate in mice.
PEGylated fluorescent microbeads were infused into the CSF space in Prox1-GFP reporter mice and decalcification histology was utilized to investigate the anatomical connections between the subarachnoid space and the lymphatic vessels in the nasal submucosa. A fluorescently-labelled antibody marking vascular endothelium was injected into the cisterna magna to demonstrate the functionality of the lymphatic vessels in the olfactory region. Finally, we performed immunostaining to study the distribution of the arachnoid barrier at the cribriform plate region.
We identified that there are open and direct connections from the subarachnoid space to lymphatic vessels enwrapping the olfactory nerves as they cross the cribriform plate towards the nasal submucosa. Furthermore, lymphatic vessels adjacent to the olfactory bulbs form a continuous network that is functionally connected to lymphatics in the nasal submucosa. Immunostainings revealed a discontinuous distribution of the arachnoid barrier at the olfactory region of the mouse.
Our data supports a direct bulk flow mechanism through the cribriform plate allowing CSF drainage into nasal submucosal lymphatics in mice.
This study was supported by the Swiss National Science Foundation (310030_189226), Dementia Research Switzerland-Synapsis Foundation, the Heidi Seiler Stiftung and the Fondation Dr. Corinne Schuler.
已确定穿过筛板延伸至鼻腔内淋巴管的嗅神经沿线是脑脊液（CSF）的重要流出途径。然而，神经沿线的流出途径如何与淋巴管连接，或者在此部位是否存在任何功能性障碍仍不清楚。本研究旨在在小鼠中解剖定义筛板处蛛网膜下腔与淋巴系统之间的连接。
将聚乙二醇化荧光微球注入 Prox1-GFP 报告小鼠的 CSF 空间，并利用脱钙组织学研究蛛网膜下腔与鼻黏膜下淋巴管之间的解剖连接。将荧光标记的血管内皮标记抗体注入枕大池以证明嗅区淋巴管的功能。最后，我们进行免疫染色以研究蛛网膜在筛板区域的分布。
我们发现，蛛网膜下腔与嗅神经交叉穿过筛板向鼻黏膜下延伸的淋巴管之间存在开放和直接的连接。此外，嗅球附近的淋巴管形成一个连续的网络，与鼻黏膜下的淋巴管功能连接。免疫染色显示，在小鼠的嗅区，蛛网膜屏障呈不连续分布。
我们的数据支持通过筛板的直接大体积流机制，允许 CSF 排入小鼠的鼻黏膜下淋巴管。
本研究得到瑞士国家科学基金会（310030_189226）、瑞士痴呆症研究-Synapsis 基金会、Heidi Seiler 基金会和 Corinne Schuler 基金会的支持。
