Englander Institute for Precision Medicine

Resolving the mysteries of brain clearance and immune surveillance.

TitleResolving the mysteries of brain clearance and immune surveillance.
Publication TypeJournal Article
Year of Publication2025
AuthorsKipnis J, Benveniste H, Eichmann A, Thomas J-L, Reich DS, Lewis LD, Tsai L-H, Drieu A, Bakker ENTP, Kelley DH, Lundgaard I, Mestre H, Zott B, Eide PKristian, van Osch MJP, van Veluw SJ, Iliff J, Yang AC, Santambrogio L, Da Mesquita S, Daneman R, Rustenhoven J, Goldman SA, Nedergaard M
JournalNeuron
Date Published2025 Nov 24
ISSN1097-4199
Abstract

Recent advances are transforming our understanding of brain fluid dynamics, highlighting cerebrospinal fluid (CSF) flow as a key process in brain waste clearance. While debates persist regarding its anatomical pathways and regulatory mechanisms, certain core principles have become widely accepted. CSF influx occurs primarily along periarterial spaces, solute clearance follows multiple routes, and glymphatic and meningeal lymphatic systems are functionally connected. Brain clearance is influenced by vascular pulsation, neural activity, and sleep. Immune cells at brain-border niches both monitor solute efflux and modulate flow, linking brain clearance to neuroimmune interactions. A deeper understanding of brain clearance could unlock new therapeutic avenues for autoimmune, neurodegenerative, neoplastic, and psychiatric disorders.

DOI10.1016/j.neuron.2025.10.036
Alternate JournalNeuron
PubMed ID41289996

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