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KAIST, 기초과학연구원

Nature, 04 June 2025 | https://doi.org/10.1038/s41586-025-09052-5 Increased CSF drainage by non-invasive manipulation of cervical lymphatics

Hokyung Jin ^1,2,9, Jin-Hui Yoon ^1,9, Seon Pyo Hong ^1,9, Yu Seok Hwang ³, Myung Jin Yang ¹, Jieun Choi ², Hae Jin Kang ¹, Seung Eun Baek¹, Cheolhwa Jin ^1,2, Junho Jung ¹, Hae Jin Kim ⁴, Jincheol Seo ⁵, Jinyoung Won ⁵, Kyung Seob Lim ⁶, Chang-Yeop Jeon ⁵, Youngjeon Lee^5,7, Michael J. Davis ⁴, Hyung-Soon Park ³, Donald M. McDonald ⁸ & Gou Young Koh ^1,2,*

¹Center for Vascular Research, Institute for Basic Science, Daejeon, Republic of Korea.
²Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea.
³Department of Mechanical Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea.
⁴Department of Medical Pharmacology and Physiology, University of Missouri, Columbia, MO, USA.
⁵National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju, Republic of Korea.
⁶Futuristic Animal Resource & Research Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju, Republic of Korea.
⁷KRIBB School of Bioscience, Korea National University of Science and Technology, Daejeon, Republic of Korea.
⁸Department of Anatomy, Cardiovascular Research Institute and Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.
⁹These authors contributed equally: Hokyung Jin, Jin-Hui Yoon, Seon Pyo Hong.

^*Corresponding author: correspondence to Gou Young Koh

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 identify. 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.

논문정보

형식Research article
게재일2025년 06월 (BRIC 등록일 2025-06-05)
연구진국내(교신)+국외 연구진
분야 생명과학 > 생리학

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