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Published on: June 6, 2015
by Lizzie Parry for The Daily News:
Scientists claim to have made a stunning discovery about the brain that ‘overturns decades of textbook teaching’ – and paves the way for a new generation of treatments for conditions such as dementia and autism.
They have discovered a ‘missing link’ between the brain and the immune system – and that the two are directly connected by vessels previously thought not to exist.
The researchers, at the University of Virginia School of Medicine, say the breakthrough could lead to new treatments for dementia, autism and other neurological disorders.
Scientists said the fact the lymphatic vessels in the brain have escaped detection when the lymphatic system has been so thoroughly mapped, is surprising in itself.
But they added, the ‘true significance’ of their discovery lies in the impact it could have on the study and treatment of neurological diseases.
In Alzheimer’s, for example, a condition is caused by a build up of proteins in the brain, the team believe these vessels play a key role in preventing the build up in healthy people.
Thus, Professor Jonathan Kipnis, who led the study, said in people with Alzheimer’s the vessels are not working correctly.
The fact they have now uncovered the existence of the vessels, means new treatments could be on the horizon.
Reflecting on their findings, Professor Kipnis, said: ‘It changes entirely the way we perceive the neuro-immune interaction.
‘We always perceived it before as something esoteric that can’t be studied. But now we can ask mechanistic questions.
‘We believe that for every neurological disease that has an immune component to it, these vessels may play a major role.
‘It’s hard to imagine that these vessels would not be involved in a [neurological] disease with an immune component.’
Researchers in his lab detected the ‘secret’ lymphatic vessels – which filter and transport fluid away from tissues before returning it to the blood – in the brains of mice.
Professor Kipnis believes they have gone unnoticed until now, because they are ‘very well hidden’, and follow a major blood vessel down to the sinuses – an area difficult to image.
Kevin Lee, who chairs the university’s department of neuroscience, described his reaction to the team’s discovery: ‘The first time these guys showed me the basic result, I just said one sentence: “They’ll have to change the textbooks”.
‘There has never been a lymphatic system for the central nervous system, and it was very clear from that first singular observation – and they’ve done many studies since then to bolster the finding – that it will fundamentally change the way people look at the central nervous system’s relationship with the immune system.’
Despite the early results, even Professor Kipnis was sceptical.
He said: ‘I really did not believe there are structures in the body that we are not aware of.
‘I thought the body was mapped.
‘I thought that these discoveries ended somewhere around the middle of last century.
‘But apparently they have not.’
He added, that now instead of asking ‘how do we study the immune response of the brain?’, scientists can approach the issue mechanistically.
He said this is ‘because the brain is like every other tissue connected to the peripheral immune system through meningeal lymphatic vessels’.
The discovery was made possible by the work of Antoine Louveau, a postdoctoral fellow in Professor Kipnis’ lab.
The vessels were detected after Louveau developed a method to mount a mouse’s meninges – the membranes covering the brain – on a single slide so that they could be examined as a whole.
‘It was fairly easy, actually,’ he said.
‘There was one trick: We fixed the meninges within the skullcap, so that the tissue is secured in its physiological condition, and then we dissected it.
‘If we had done it the other way around, it wouldn’t have worked.’
After noticing vessel-like patterns in the distribution of immune cells on his slides, he tested for lymphatic vessels and discovered they were there.
The impossible existed.
Dr Louveau recalled the moment: ‘I called Jony [Professor Kipnis] to the microscope and I said, “I think we have something”.
As to how the brain’s lymphatic vessels managed to escape notice all this time, Professor Kipnis, said: ‘It’s so close to the blood vessel, you just miss it.
‘If you don’t know what you’re after, you just miss it.
‘Live imaging of these vessels was crucial to demonstrate their function, and it would not be possible without collaboration with Tajie Harris,’ Kipnis noted.
Dr Harris is an assistant professor of neuroscience and a member of the Center for Brain Immunology and Glia.
The unexpected presence of the lymphatic vessels raises a tremendous number of questions that now need answers, both about the workings of the brain and the diseases that plague it, researchers said.
For example, Professor Kipnis said, take Alzheimer’s disease.
‘In Alzheimer’s, there are accumulations of big protein chunks in the brain,’ he said.
‘We think they may be accumulating in the brain because they’re not being efficiently removed by these vessels.’
He noted that the vessels look different with age, so the role they play in ageing is another avenue to explore.
And there’s an enormous array of other neurological diseases, from autism to multiple sclerosis, that must be reconsidered in light of the presence of something science insisted did not exist.
Professor Kipnis also saluted the ‘phenomenal’ surgical skills of Igor Smirnov, a research associate in the Kipnis lab whose work was critical to the imaging success of the study.
The findings have been published online in the journal Nature.
Picture: Scientists at the University of Virginia have discovered lymphatic vessels in the brain, which were previously thought not to exist. Lymphatic vessels work to filter and transport fluid away from tissues before returning it to the blood. Pictured left, is the map of the lymphatic system before the discovery, and right, after the findings.
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