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Cell, Available online 21 July 2026 | https://doi.org/10.1016/j.cell.2026.06.035 CSF clearance through arachnoid fenestrations to olfactory meningeal lymphatics

Seon Pyo Hong^1,8, Cheolhwa Jin ^1,2,8, Myung Jin Yang ¹, Hokyung Jin ¹, Jin-Hui Yoon ^1,7, Du Ri Choi ¹, Junho Jung ¹, Chae Min Yuk ¹, Salli Antila³, Su Jin Seo¹, Leul A. Admasu ^1,2, Jincheol Seo ⁴, Kyung Seob Lim ⁵, Won-Suk Chung ¹, Kari Alitalo ³, Donald M. McDonald ⁶, Gou Young Koh^1,2,9

¹Center for Vascular Research, Institute for Basic Science, Daejeon 34141, Republic of Korea
²Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea
³Wihuri Research Institute and Translational Cancer Medicine Program, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland
⁴National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju 28116, Republic of Korea
⁵Futuristic Animal Resource & Research Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju 28116, Republic of Korea
⁶Department of Anatomy, Cardiovascular Research Institute and Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94143-0452, USA
⁷Present address: Department of Brain Science and Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea
⁸These authors contributed equally
⁹Lead contact

Corresponding authors: Seon Pyo Hong, Donald M. McDonald, Gou Young Koh

Abstract

Meningeal (dural) lymphatics are essential for cerebrospinal fluid (CSF) clearance to cervical lymph nodes, yet the precise pathway is incompletely understood. Using a multifaceted approach in mice, we examined tracer dynamics and the CSF outflow pathway from the subarachnoid space (SAS) to the nasal mucosa and identified a discrete arachnoid region surrounding the olfactory bulbs with abundant fenestrations. Similar arachnoid fenestrations were found in cynomolgus monkeys. Fluorescent tracers in the SAS passed through arachnoid fenestrations into dural lymphatics, which traversed the cribriform plate foramina, joined the nasal lymphatics, and drained to the cervical lymph nodes. In aged mice, the known reduction in CSF outflow was accompanied by lymphatic atrophy in the olfactory dura and nasal mucosa and by fewer arachnoid fenestrations and smaller cribriform plate foramina. Importantly, the lymphatics and CSF clearance were restored to normal by intranasal delivery of vascular endothelial growth factor-C (VEGF-C), thereby documenting the reversibility of the aging-related impairment in CSF clearance.

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