鼻咽淋巴管丛是脑脊液引流的枢纽。

Nasopharyngeal lymphatic plexus is a hub for cerebrospinal fluid drainage.

机构信息

Center for Vascular Research, Institute for Basic Science, Daejeon, Republic of Korea.

Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea.

出版信息

Nature. 2024 Jan;625(7996):768-777. doi: 10.1038/s41586-023-06899-4. Epub 2024 Jan 10.

Abstract

Cerebrospinal fluid (CSF) in the subarachnoid space around the brain has long been known to drain through the lymphatics to cervical lymph nodes, but the connections and regulation have been challenging to identify. Here, using fluorescent CSF tracers in Prox1-GFP lymphatic reporter mice, 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. α-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.

摘要

脑脊髓液(CSF)在大脑周围的蛛网膜下腔中早已被发现通过淋巴系统排入颈部淋巴结,但连接和调节一直难以确定。在这里,我们使用 Prox1-GFP 淋巴报告小鼠中的荧光 CSF 示踪剂,发现鼻咽淋巴丛是 CSF 流出到深部颈淋巴结的主要枢纽。该丛具有不寻常的瓣膜和短淋巴管,但没有平滑肌覆盖,而下游深部颈淋巴管具有典型的半月形瓣膜、长淋巴管和平滑肌覆盖,可将 CSF 输送到深部颈淋巴结。平滑肌细胞中的α-肾上腺素能和一氧化氮信号调节 CSF 通过深部颈淋巴管的转运特性进行引流。在衰老过程中,鼻咽淋巴丛萎缩,但深部颈淋巴管没有类似的改变,通过肾上腺素能或一氧化氮信号仍可以增加 CSF 外流。对老年小鼠鼻咽丛淋巴管内皮细胞的单细胞分析显示,I 型干扰素信号和其他炎症细胞因子增加。鼻咽淋巴丛作为 CSF 流出枢纽的证据的重要性,突出表现在其在衰老过程中的退化。然而,对深部颈淋巴转运向淋巴结的衰老抵抗性药物激活仍可增加 CSF 外流,为在与年龄相关的神经疾病中增加 CSF 清除提供了一种方法,因为在这些疾病中,更大的流出量将是有益的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19f5/10808075/84ec985ab19a/41586_2023_6899_Fig1_HTML.jpg

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