Brain's drainage veins actively pump immune cells, study finds

Brain's drainage system is far more active than thought

Large veins that drain fluid from the brain are not passive pipes but dynamic, pulsing structures that actively pump and rearrange themselves to accommodate immune cells, according to a new study in Nature. The research, conducted in mice and humans, fundamentally changes the understanding of the brain's protective borders.

The veins, called venous sinuses, sit within the outermost meningeal membrane. Using a technique called intravital imaging on live mice, researchers observed these vessels constricting and dilating to actively move fluid. "Having studied vessels now for over 20 years, I’ve never seen a vessel do that before," says co-author Dorian McGavern, a neuroimmunologist at the National Institute of Neurological Disorders and Stroke.

Observing the brain's unique plumbing

The research team thinned a small section of a mouse's skull to make it transparent, allowing a laser to illuminate fluorescently-labeled immune cells beneath. This revealed the venous sinuses, wrapped in smooth muscle, pulsing underneath the skull.

The team also captured stop-motion videos of the endothelial cells that form the vein walls. These cells contain tiny holes, called fenestrations, that allow the passage of fluid, molecules, and microorganisms. Most strikingly, the vessel borders were in constant motion.

"These junctions were opening and closing constantly, and this is basically driven by immune cells that are sniffing around the sinus wall all the time," McGavern says. The researchers dubbed this constant reshaping "ruffling."

A dynamic border for brain protection

The discovery positions the brain's borders as highly regulated interfaces, not simple anatomical coverings. Jonathan Kipnis, a neuroimmunologist at Washington University School of Medicine in St. Louis who was not involved in the study, calls the work "rigorous and technically sophisticated."

This active system is crucial for protecting the delicate central nervous system. Any buildup of inflammation, fluid, or pressure under the skull can quickly become dangerous. The sinuses appear to help preserve brain function by actively responding to these threats.

"The endothelial cells are pliable in a way that is very, very unique," McGavern adds. The study's key findings include:

• Venous sinuses actively pump blood and cerebrospinal fluid.
• Vessel walls constantly "ruffle" to let immune cells patrol.
• Endothelial cells contain fenestrations up to one micrometre in diameter.
• This dynamic activity is observed in both mice and humans.

Redefining basic brain anatomy

The research suggests a complete revision of a fundamental anatomical concept. The venous sinuses, long considered a passive drainage network, are now seen as a primary site of immune activity and fluid regulation for the brain.

This has broad implications for understanding how the brain manages waste, fights infection, and maintains its carefully balanced environment. The study supports the growing view that the borders separating the brain from the rest of the body are complex, active immunological sites.

Future research will likely investigate how failures in this "ruffling" or pumping activity might contribute to neurological diseases involving inflammation, fluid buildup, or impaired waste clearance.