Research News

A first-of-its-kind neurodevelopment study from the neuroscience research lab of Antoine Louveau, PhD, has identified that the meningeal lymphatic vessels—a system of structures outside the brain—can influence how the brain functions.

The results of the study, published in Neuron, shed new light on this little-known system around the brain. The vessels, which are part of the lymphatic system, function as drainage pathways to clear fluid and support immune activity. Previous studies on the lymphatic system have mainly focused on the effects of neurodegeneration, or the progressive loss of neuron function and brain structure, instead of on how the system is built and how it influences brain function over a lifetime.

Dr. Louveau, whose lab studies structures he describes as “on the borders of the brain,” is taking a different approach.

Neurodevelopment and pruning

The lymphatic system includes lymphatic vessels, which run throughout the body and into the meninges—protective layers of tissue between the brain and the skull. Dr. Louveau was first author on the 2015 Nature paper that introduced the meningeal lymphatic vessels, and researchers have continued to learn more about their structure and function over the past decade.

They have noted that when these vessels are developing (which is thought to be during late pregnancy or early infancy), the vessels grow rapidly and overpopulate on purpose. Then, the extra branches are methodically “pruned” away.

“That pruning process is controlled by immune cells, or macrophages,” Dr. Louveau explains. “It’s a two-step biological process where excess lymphatic cells are programmed to die and macrophages ‘clean up’ by engulfing them. But if that pruning process doesn’t occur properly, a person is left with an overly complex lymphatic system that persists into adulthood.”

Biological and neuroscientific relevance

The team’s research, as highlighted in the Neuron article, examined the vessels’ development and pruning in a preclinical model of severe neurodevelopmental impairment. Not only did they discover that pruning did not occur properly, they also noticed a connection between the remaining overgrowth and differences in expected social behavior.

This new scientific insight suggests that these vessels develop in a way unlike the lymphatic vessels in other places throughout the body. In other words, the vessels behave like the brain, even though they are outside of the brain—and development (whether typical or atypical) can have a noticeable effect on behavior.

Back to the beginning

Dr. Louveau believes that the key to truly understanding the meningeal lymphatic vessels is to study their early phases of development—an approach that, up to this point, has mostly been applied to research on Alzheimer’s disease and multiple sclerosis.

“Understanding how these meningeal lymphatic vessels grow, as well as their typical function and processes, is the only way we will develop tools to refine when something is atypical,” he says. “This study revealed that these vessels are not inert. They do more than physically protect the brain; they also communicate with and influence it.”

“If we can develop a therapeutic that targets the lymphatic vasculature—without even touching the brain—we could potentially improve neuron function.”