The brain’s sewerage system — a network of large veins embedded in a membrane close to the skull — does not contain passive vessels as it was once thought.
The delicate brain is protected from physical damage and invading pathogens by three (3) layers of membrane called the meninges. Large veins called the venous sinuses, which sit in the outermost membrane, help to drain fluid from the brain and skull, but their full range of activities has been unclear until now. In a study in mice and humans published in Nature in February 2026, researchers captured the venous sinuses pumping blood and cerebrospinal fluid. The vessels also continuously shuffled their cells around to accommodate for patrolling immune cells.
The study supports the idea that brain borders are highly regulated interfaces rather than simple anatomical coverings, says Jonathan Kipnis, a Neuroimmunologist at Washington University School of Medicine in St. Louis. It is “rigorous and technically sophisticated”, he adds.
The dynamic nature of the venous sinuses is important for protecting the central nervous system, says Dorian McGavern, a Neuroimmunologist at the National Institute of Neurological Disorders and Stroke in Bethesda, Maryland, and a Co-Author of the paper. Any build-up of inflammation, fluid or pressure under the skull can quickly endanger the brain, and the sinuses could help to preserve brain function by actively responding to these threats, he says.
Live action
The research team recorded the activity of venous sinuses in live, anaesthetized mice by whittling down a square millimeter of the skull until it was thin enough for a laser to pass through it, illuminating the immune cells, which were labelled with a fluorescent protein, beneath. Using this technique, called “intravital imaging”, large veins wrapped in smooth muscle could be observed pulsing underneath the skull, constricting and dilating to actively drain fluid.
The researchers created stop-motion videos of the endothelial cells that make up the vein walls and observed that they contain small holes up to one micrometer in diameter, known as fenestrations, which allow the passage of fluid, molecules and microorganisms. Veins were also able to rearrange their borders to accommodate surveying immune cells. The researchers called this strange behavior ruffling.
“Having studied vessels now for over 20 years, I’ve never seen a vessel do that before,” says McGavern. “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,” he says. “The endothelial cells are pliable in a way that is very, very unique.”
The study found that human sinuses are also wrapped in a layer of smooth muscle and have similar porosity to mouse sinuses. The ruffling of cells, however, could not be shown in humans because current non-invasive imaging methods do not provide the resolution needed to observe that behavior in living people, says McGavern.
When the Researchers blocked a receptor called RAMP2, the mice had a hard time fighting off a viral infection. As a result, their sinuses behaved like passive vessels and reduced the activity of immune cells. This suggests that the immune cells moving along the vein walls play an important part in viral defense, says McGavern.
The team also report that the neuropeptide CGRP dilated the veins. It is possible that migraine medications called CGRP inhibitors could work in part by changing the activity of the sinuses, says McGavern.
REFERENCE: Nature; 18 FEB 2026; Felicity Nelson