Groundbreaking research from the National Institutes of Health (NIH) shows that the brain has lymphatic vessels, allowing it to process “waste” leaked from the blood vessels. This may shed fresh light on the relationship between the brain and the immune system.
The body’s lymphatic system relies on lymphatic vessels to absorb, process, and return proteins and interstitial fluid – that is, the fluid that surrounds tissue cells in the body – to the bloodstream. The fluid carried by the lymphatic vessels is called “lymph.”
There are three main functions of the lymphatic system: to help keep blood volume and pressure constant, to fight foreign agents as part of the immune system, and to absorb fat and fat-soluble vitamins.
Lymphatic vessels are distributed throughout our bodies, but so far, there has been little evidence to suggest that the brain also contains them. In a medical treatise from 1816, an Italian scientist suggested the existence of such vessels, but this notion was rejected until fairly recently.
Now, a team of researchers from the National Institutes of Health (NIH) – led by Dr. Daniel S. Reich – has confirmed that human brains also have lymphatic vessels. More specifically, they were noted in the dura, or the thick outermost membrane that surrounds the brain.
“We literally watched people’s brains drain fluid into these vessels,” says Dr. Reich. “We hope that our results provide new insights to a variety of neurological disorders.”
The researchers’ findings have recently been reported in the journal eLife.
Dr. Reich and team used noninvasive methods to ascertain the presence of lymphatic vessels in the human brain.
They worked with five healthy volunteers and three marmoset monkeys whose brains were scanned using MRI, following injections with different kinds of contrast agents.
These are substances stand “stand out” during an MRI scan, thus allowing scientists to better visualise blood vessels in the brain.
First, the researchers injected the volunteers with gadobutrol, the molecules of which are small enough to leak out of the blood vessels and into the interstitial compartment of the brain.
The initial MRI scan only highlighted the blood vessels in the dura, but some additional imaging adjustments also revealed thinner highlighted lines. These, the researchers hypothesized, were lymphatic vessels that had picked up the contrasting agent that had leaked out of the blood vessels.
Next, Dr. Reich and team decided to test their hypothesis by injecting one human participant and one monkey with gadofosveset. This is another contrasting agent made up of larger molecules, which minimized the possibility that these would leak out of the blood vessels.
As expected, new MRI scans showed the highlighted blood vessels but revealed no trace of other kinds of vessels.
This, the researchers explain, suggests that their hypothesis was correct: there are lymphatic vessels in the dura that pick up fluid elements from the interstitial compartment of the brain.
Some evidence of the existence of lymphatic vessels was also found in three autopsied human brains. Two of the samples were collected from the duras of a 60- and a 77-year-old with progressive multiple sclerosis (MS), and one from a 33-year-old with refractory epilepsy.
“For years,” says Dr. Reich, “we knew how fluid entered the brain. Now we may finally see that, like other organs in the body, brain fluid can drain out through the lymphatic system.”
Dr. Reich and colleagues are next hoping to investigate what implications their findings bear from a clinical perspective. For instance, they would like to see whether, or how, the lymphatic system functions – or malfunctions – in people diagnosed with neuroinflammatory conditions such as MS.
“These results could fundamentally change the way we think about how the brain and immune system inter-relate.”
Dr. Walter J. Koroshetz, National Institute of Neurological Disorders and Stroke