基础科学研究所Gou Young Koh研究小组近日取得一项新成果。经过不懈努力，他们报道了通过无创操作颈淋巴增加脑脊液引流。这一研究成果发表在2025年6月4日出版的国际学术期刊《自然》上。

在此，该研究组在Prox1-GFP淋巴报告小鼠中使用荧光示踪剂来绘制脑脊液流出经淋巴到颈部浅表淋巴结的途径。脑脊液进入颅底脑膜的初始淋巴管，经颅外眶周淋巴管、嗅淋巴管、鼻咽淋巴管和硬腭淋巴管，再经光滑的颈浅淋巴管至下颌下淋巴结。在成年小鼠中进行的示踪研究显示，大量的脑脊液流出到颈部，流向颈部浅表淋巴结。

然而，老年小鼠鼻黏膜和硬腭的淋巴管减少，脑脊液向颈部淋巴结的流出量减少。老年小鼠颈部淋巴细胞表面编码内皮型一氧化氮合酶（eNOS）的内皮细胞Nos3表达增加，但eNOS蛋白表达减少，一氧化氮信号传导受损。用力调节机械装置通过完整皮肤操纵颈部浅表淋巴，使老年小鼠脑脊液流出量增加一倍，并纠正了引流损伤。这种手法通过压迫颈浅淋巴增加脑脊液流出，而对其正常的自发收缩几乎没有影响。总的来说，研究结果强调了颈浅淋巴对脑脊液流出的重要性，以及通过非侵入性机械刺激逆转脑脊液引流障碍的潜力。

据了解，脑脊液（CSF）在脑周围的蛛网膜下腔中流向颈部淋巴结，但其连接和调节一直具有挑战性，难以确定。

附：英文原文

Title: Increased CSF drainage by non-invasive manipulation of cervical lymphatics

Author: Jin, Hokyung, Yoon, Jin-Hui, Hong, Seon Pyo, Hwang, Yu Seok, Yang, Myung Jin, Choi, Jieun, Kang, Hae Jin, Baek, Seung Eun, Jin, Cheolhwa, Jung, Junho, Kim, Hae Jin, Seo, Jincheol, Won, Jinyoung, Lim, Kyung Seob, Jeon, Chang-Yeop, Lee, Youngjeon, Davis, Michael J., Park, Hyung-Soon, McDonald, Donald M., Koh, Gou Young

Issue&Volume: 2025-06-04

Abstract: Cerebrospinal fluid (CSF) in the subarachnoid space around the brain drains to lymph nodes in the neck, but the connections and regulation have been challenging to identify1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24. Here we used fluorescent tracers in Prox1–GFP lymphatic reporter mice to map the pathway of CSF outflow through lymphatics to superficial cervical lymph nodes. CSF entered initial lymphatics in the meninges at the skull base and continued through extracranial periorbital, olfactory, nasopharyngeal and hard palate lymphatics, and then through smooth muscle-covered superficial cervical lymphatics to submandibular lymph nodes. Tracer studies in adult mice revealed that a substantial amount of total CSF outflow to the neck drained to superficial cervical lymph nodes. However, aged mice had fewer lymphatics in the nasal mucosa and hard palate and reduced CSF outflow to cervical lymph nodes. Superficial cervical lymphatics in aged mice had increased endothelial cell expression of Nos3, encoding endothelial nitric oxide synthase (eNOS), but had less eNOS protein and impaired nitric oxide signalling. Manipulation of superficial cervical lymphatics through intact skin by a force-regulated mechanical device doubled CSF outflow and corrected drainage impairment in aged mice. This manipulation increased CSF outflow by compressing superficial cervical lymphatics while having little effect on their normal spontaneous contractions. Overall, the findings highlight the importance of superficial cervical lymphatics for CSF outflow and the potential for reversing CSF drainage impairment by non-invasive mechanical stimulation.

DOI: 10.1038/s41586-025-09052-5

Source: https://www.nature.com/articles/s41586-025-09052-5