'Missing link' between brain and immune system discovered

“Newly discovered vessels beneath skull could link brain and immune system,” The Guardian reports. It is has been suggested that the discovery, which has been described as textbook-changing, could lead to new treatments for a range of neurological conditions.

Until now, it was thought that the brain was not connected to the lymphatic system. This is an essential part of the immune system that helps fight infection, while draining excess fluid from tissue.

In this study, scientists discovered previously unknown lymphatic vessels in the outer layers of the brain. These vessels appeared to link the brain and spinal cord with the rest of the body’s immune system. This study used mice and human samples, vessel structure was investigated in the mice, and the observations followed up in the human samples.

Further study will be needed to confirm that the system works the same in humans, but the discovery may require a reassessment of our assumptions about lymph drainage in the brain and its role in diseases involving brain inflammation or degeneration, such as Alzheimer’s disease and multiple sclerosis.

It is too early to say whether the findings could one day have any implications for the treatment of these types of conditions.

Where did the story come from?

The study was carried out by researchers from The University of Virginia and was funded by Fondation pour la Recherche Médicale and by The National Institutes of Health. The study was published in the peer-reviewed scientific journal Nature.

The study has generated a great deal of media excitement, both in the UK and internationally.

This excitement seems largely driven by quotes released by the researchers themselves, such as Professor Kevin Lee, who was widely quoted as saying: “The first time these guys showed me the basic result, I just said one sentence: ‘They’ll have to change the textbooks’.”

However, media reports, such as the Mail Online stating that “[the discovery] could help treat conditions such as autism and Alzheimer’s” is premature, and cannot be concluded from this stage of the research.

What kind of research was this?

This was an animal study using mice to investigate the structure and function of lymphatic vessels in the brain.

It is said to have been previously understood that the central nervous system (brain and spinal cord) did not have a typical lymphatic drainage system. Lymph is the immune fluid that circulates round the body, containing white blood cells to fight infection and destroy abnormal cells.

This study aimed to look at the circulation of lymph in the mouse brain, potentially creating a greater understanding of the workings of the brain and disease processes. However, mice and humans do not have identical biology, so the findings may not be directly applicable. 

What did the research involve?

The scientists used adult mice to look at brain structure and the circulation of lymph.

The study involved complex laboratory techniques. This included the use of a fluorescent antibody to assess the alignment of cells within the brain, examination for markers associated with a lymphatic drainage system and looking at the functional capacity of identified vessels to carry lymphatic fluid to and from the brain. 

Human samples taken from the brain at autopsy were used to investigate any structures found in mice.

What were the basic results?

The scientists found that the outer protective layers of the mouse brain (the meninges) showed cells that were clearly lined up, which suggested that these were vessels with a unique function. These cells showed the characteristic features of functional lymphatic vessels. These vessels appeared able to carry both fluid and immune cells from the fluid surrounding the brain and spinal cord (the cerebrospinal fluid), and were connected to the lymph nodes in the neck.

The location of these vessels may have been the reason they have not been discovered to-date, thereby causing the belief that there is no lymphatic drainage system in the brain.

How did the researchers interpret the results?

The researchers state: “The presence of a functional and classical lymphatic system in the central nervous system [brain and spinal cord] suggests that current dogmas regarding brain tolerance and the immune privilege of the brain should be revisited”. This new understanding may mean current thinking about how the brain works needs to be reassessed. The researchers go on to say it could be the malfunction of these vessels that could be the cause of a variety of brain disorders, such as multiple sclerosis and Alzheimer’s disease.

Conclusion

This mouse study has examined the circulation of lymph in the brain. It discovered previously unknown lymphatic vessels in the outer layers of the mouse brain. If accurate, the findings may call for a review of how the immune system in the brain functions, and shed new light on its role in brain diseases involving brain inflammation or degeneration.

Though animal research can give a good insight into biological and disease processes, and how they may work in humans, the processes in humans and mice are not identical. Further studies are needed to confirm these findings and to assess whether this knowledge is transferable to humans.

As such, it is too early to say whether the findings could one day have any implications for the treatment of degenerative brain conditions such as multiple sclerosis or Alzheimer’s.