By scanning the brains of healthy volunteers, scientists have found the first, long-sought evidence that our brains may drain out some waste through lymphatic vessels, the body's sewer system.
The research suggests that the vessels could act as a pipeline between the brain and the immune system.
"We literally watched peoples brains drain fluid into these vessels," said Daniel S Reich, from the National Institute of Neurological Disorders and Stroke (NINDS) in the US.
"We hope that our results provide new insights to a variety of neurological disorders," said Reich, senior author of the study published in the journal eLife.
Along with researchers from the National Cancer Institute in the US, the team discovered lymphatic vessels in the dura, the leathery outer coating of the brain.
Lymphatic vessels are part of the body's circulatory system. In most of the body they run alongside blood vessels. They transport lymph, a colourless fluid containing immune cells and waste, to the lymph nodes.
Blood vessels deliver white blood cells to an organ and the lymphatic system removes the cells and recirculates them through the body.
The process helps the immune system detect whether an organ is under attack from bacteria or viruses or has been injured.
In 1816, an Italian anatomist reported finding lymphatic vessels on the surface of the brain, but for two centuries, it was forgotten, researchers said.
Reichs team used magnetic resonance imaging (MRI) to scan the brains of five healthy volunteers who had been injected with gadobutrol, a magnetic dye typically used to visualise brain blood vessels damaged by diseases, such as multiple sclerosis or cancer.
The dye molecules are small enough to leak out of blood vessels in the dura but too big to pass through the blood- brain barrier and enter other parts of the brain.
At first, when the researchers set the MRI to see blood vessels, the dura lit up brightly, and they could not see any signs of the lymphatic system.
However, when they tuned the scanner differently, the blood vessels disappeared, and the researchers saw that dura also contained smaller but almost equally bright spots and lines which they suspected were lymph vessels.
The results suggested that the dye leaked out of the blood vessels, flowed through the dura and into neighbouring lymphatic vessels.
To test this idea, the researchers performed another round of scans on two subjects after first injecting them with a second dye made up of larger molecules that leak much less out of blood vessels.
In contrast with the first round of scans, researchers saw blood vessels in the dura but no lymph vessels regardless of how they tuned the scanner, confirming their suspicions.
They also found evidence for blood and lymph vessels in the dura of autopsied human brain tissue.
Moreover, their brain scans and autopsy studies of brains from nonhuman primates confirmed the results seen in humans, suggesting the lymphatic system is a common feature of mammalian brains.
"These results could fundamentally change the way we think about how the brain and immune system inter-relate," said Walter J Koroshetz, NINDS director.