Nasopharyngeal lymphatic plexus is a hub for cerebrospinal fluid drainage

• 成果类型: Article
• 署名作者: Yoon, Jin-Hui; Jin, Hokyung; Kim, Hae Jin; Hong, Seon Pyo; Yang, Myung Jin; Ahn, Ji Hoon; Kim, Young-Chan; Seo, Jincheol; Lee, Yongjeon; Mcdonald, Donald M.; Davis, Michael J.; Koh, Gou Young
• 署名单位: Institute for Basic Science - Korea (IBS); Korea Advanced Institute of Science & Technology (KAIST); University of Missouri System; University of Missouri Columbia; Korea Research Institute of Bioscience & Biotechnology (KRIBB); University of California System; University of California San Francisco; University of California System; University of California San Francisco; UCSF Medical Center; UCSF Helen Diller Family Comprehensive Cancer Center
• 刊物名称: Nature
• ISSN/ISSBN: 0028-3752
• DOI: 10.1038/s41586-023-06899-4
• 发表日期: 2024-01-25
• 关键词: subarachnoid injection; nasal lymphatics; rat; vessels; connections; mechanisms; transport; SYSTEM; SPACE

摘要

Cerebrospinal fluid (CSF) in the subarachnoid space around the brain has long been known to drain through the lymphatics to cervical lymph nodes1-17, but the connections and regulation have been challenging to identify. Here, using fluorescent CSF tracers in Prox1-GFP lymphatic reporter mice18, we found that the nasopharyngeal lymphatic plexus is a major hub for CSF outflow to deep cervical lymph nodes. This plexus had unusual valves and short lymphangions but no smooth-muscle coverage, whereas downstream deep cervical lymphatics had typical semilunar valves, long lymphangions and smooth muscle coverage that transported CSF to the deep cervical lymph nodes. alpha-Adrenergic and nitric oxide signalling in the smooth muscle cells regulated CSF drainage through the transport properties of deep cervical lymphatics. During ageing, the nasopharyngeal lymphatic plexus atrophied, but deep cervical lymphatics were not similarly altered, and CSF outflow could still be increased by adrenergic or nitric oxide signalling. Single-cell analysis of gene expression in lymphatic endothelial cells of the nasopharyngeal plexus of aged mice revealed increased type I interferon signalling and other inflammatory cytokines. The importance of evidence for the nasopharyngeal lymphatic plexus functioning as a CSF outflow hub is highlighted by its regression during ageing. Yet, the ageing-resistant pharmacological activation of deep cervical lymphatic transport towards lymph nodes can still increase CSF outflow, offering an approach for augmenting CSF clearance in age-related neurological conditions in which greater efflux would be beneficial. The nasopharyngeal lymphatic plexus is a major hub for cerebrospinal fluid outflow to deep cervical lymph nodes.