How Our Brain Drains Its Waste Products

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Dec 21, 2025

Jonathan Kipnis, a leading neuroscientist at Washington University, discusses groundbreaking findings about the brain's waste clearance system. He explains how meningeal lymphatics challenge the belief that the brain lacks a drainage system. Listeners will find insight into glymphatic flow, the role of astrocytes, and how sleep enhances waste removal. Kipnis also highlights the connection between immune surveillance and brain health, diving into how aging and autoimmune diseases affect lymphatic function and potential therapeutic approaches.

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INSIGHT

Meningeal Lymphatics Exist And Matter

The brain has a lymphatic-like sewage system outside the parenchyma in the meninges that drains waste to lymph nodes.
Jonathan Kipnis discovered meningeal lymphatics, overturning the long-held view that the brain lacked lymphatic drainage.

INSIGHT

CSF Washes Brain And Feeds Immune Surveillance

Cerebrospinal fluid (CSF) moves into and through brain tissue to wash out metabolites and proteins like beta-amyloid.
That interstitial efflux ultimately reaches meningeal lymphatics which present material to immune surveillance.

INSIGHT

Multiple Forces Control Glymphatic Flow

Glymphatic flow is modulated by arterial pulsation, respiration/venous dynamics, vasomotion, astrocyte volume, and perivascular macrophages.
Perivascular macrophages maintain vessel compliance by clearing extracellular matrix and thus influence fluid pumping.

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Jonathan Kipnis is a neuroscientist, the Alan A. and Edith L. Wolff Distinguished Professor of Pathology and Immunology at Washington University, St. Louis, who discovered meningeal lymphatics and has been a prolific researcher in brain drainage and the continuous immune system surveillance of the brain.

I made this infographic with the help of Notebook LM to summarize many of the concepts we discussed. (Notebook LM is free and worth trying)

We went over his new review with 24 co-author leading experts in the recent issue of Neuron

A Clever Cover

The drainage system anatomy on influx and efflux (blue arrows)

The 3 ways the flow of glymphatics are modulated. I mentioned the recent studies that show atrial fibrillation, via reduced cardiac pulsation, has an effect on reducing glymphatic flow.

We also discussed his recent review on the immune surveillance system in Cell:

A schematic of key channels for the “faucet” and “drain”

and how the system changes from healthy to central nervous system autoimmune diseases (such as multiple sclerosis) and aging with different immune bar codes.

The outsized role of astrocytes in the brain, a subject of recent Nature feature, was also mentioned.

Our understanding of the brain’s immune system has been completely revamped. Kipnis’s recent review in Nature Immunology highlights the critical role of the outer layers —the skull, dura and meninges—as an immune reservoir that is ready to detect and react abnormalities in the brain with a continuous “intelligence report.”

Notably, Kipnis touched on lymphatic-venous anastomosis (LVA) surgery (Figure below) for Alzheimer’s disease which is popular in China, available at 30 centers in multiple cities, and the subject of multiple randomized trials as a treatment for Alzheimer’s. Trials of LVA surgery are also getting started in the United States for treatment of Alzheimer’s and Parkinson’s diseases.

Here is a Figure to show the surgical anastomoses (connections) from the deep cervical lymphatics to external jugular and internal jugular veins

This podcast was packed with insights relevant to health, spanning sleep quality, sleep medications, autoimmune diseases, and Alzheimer’s disease. I hope you find it as informative and engaging as I did.

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