Department of Neurology, Saarland University Medical Center, Homburg, Germany.
Theodor Kocher Institute, University of Bern, Bern, Switzerland.
JCI Insight. 2022 Feb 8;7(3):e150881. doi: 10.1172/jci.insight.150881.
The anatomical routes for the clearance of cerebrospinal fluid (CSF) remain incompletely understood. However, recent evidence has given strong support for routes leading to lymphatic vessels. A current debate centers upon the routes through which CSF can access lymphatics, with evidence emerging for either direct routes to meningeal lymphatics or along cranial nerves to reach lymphatics outside the skull. Here, a method was established to infuse contrast agent into the ventricles using indwelling cannulae during imaging of mice at 2 and 12 months of age by magnetic resonance imaging. As expected, a substantial decline in overall CSF turnover was found with aging. Quantifications demonstrated that the bulk of the contrast agent flowed from the ventricles to the subarachnoid space in the basal cisterns. Comparatively little contrast agent signal was found at the dorsal aspect of the skull. The imaging dynamics from the 2 cohorts revealed that the contrast agent was cleared from the cranium through the cribriform plate to the nasopharyngeal lymphatics. On decalcified sections, we confirmed that fluorescently labeled ovalbumin drained through the cribriform plate and could be found within lymphatics surrounding the nasopharynx. In conclusion, routes leading to nasopharyngeal lymphatics appear to be a major efflux pathway for cranial CSF.
脑脊液(CSF)清除的解剖途径仍不完全清楚。然而,最近的证据强烈支持通向淋巴管的途径。目前的争论集中在 CSF 进入淋巴管的途径上,有证据表明 CSF 可以通过直接途径进入脑膜淋巴管,也可以通过颅神经到达颅骨外的淋巴管。在这里,建立了一种方法,即在磁共振成像(MRI)对 2 个月和 12 个月大的小鼠进行成像时,使用留置套管将造影剂注入脑室。正如预期的那样,随着年龄的增长,脑脊液总体周转率显著下降。定量分析表明,大部分造影剂从脑室流到基底池的蛛网膜下腔。在颅骨的背面相对较少的造影剂信号被发现。来自 2 个队列的成像动力学表明,造影剂通过筛板从颅骨清除到鼻咽淋巴管。在脱钙切片上,我们证实荧光标记的卵清蛋白通过筛板排出,并可在围绕鼻咽的淋巴管中找到。总之,通向鼻咽淋巴管的途径似乎是颅 CSF 的主要流出途径。