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In a stunning discovery that overturns decades of textbook teaching, researchers at the University of Virginia School of Medicine have determined that the brain is directly connected to the immune system by vessels previously thought not to exist.

That such vessels could have escaped detection when the lymphatic system has been so thoroughly mapped throughout the body is surprising on its own, but the true significance of the discovery lies in the effects it could have on the study and treatment of neurological diseases ranging from autism to Alzheimer’s disease to multiple sclerosis.

Jonathan Kipnis said the discovery will change the way scientists study neuro-immune interaction.

“Instead of asking, ‘How do we study the immune response of the brain?,’ ‘Why do multiple sclerosis patients have the immune attacks?,’ now we can approach this mechanistically – because the brain is like every other tissue connected to the peripheral immune system through meningeal lymphatic vessels,” said Jonathan Kipnis, a professor in U.Va.’s Department of Neuroscience and director of U.Va.’s Center for Brain Immunology and Glia. “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."

He added, “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.”

Kevin Lee, who chairs the Department of Neuroscience, described his reaction to the discovery by Kipnis’ lab: “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 – which it will fundamentally change the way people look at the central nervous system’s relationship with the immune system.”

Even Kipnis was skeptical initially. “I really did not believe there are structures in the body that we are not aware of. I thought the body was mapped,” he said. “I thought that these discoveries ended somewhere around the middle of the last century. But apparently they have not.”

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  • This is interesting and certainly one to watch. Thanks for sharing it, Liberton. :)

    We're a long way off knowing what the significance of this finding is. It is worth noticing that this is a science story that has made it into the news before the research has actually been published, so no-one other than the research team has seen the full details; and it's always wise to take scientists' own claims about their findings with a pinch of salt (after all, they're hardly going to say "Oh, my life's work so far is completely pointless; I haven't found ANYTHING interesting!" ;) )

    It looks like, for sure, they have discovered a pathway between the brain and the immune system that noone has found before, and they have found immune cells in the brains of healthy mice. This is significant because previously immune cells have only been found in diseased brains, and noone could explain why. Now there's a known route for immune cells to reach the brain, it is theoretically possible to do all sorts of other studies to find out how this works, and to try to work out if and how the immune system might affect the brain and/or vice versa. It's much too soon to guess what those findings might be...

    I look forward to seeing the full research report. Meanwhile, the original article that sparked all this interest (it's a letter published in Nature) is behind a paywall here: nature.com/nature/journal/v...

    There is a reasonably clear summary here: nih.gov/news-events/nih-res...

    And there is an article that explains why it might be important here: the-scientist.com/?articles...

  • Thanks for these links Flow. I've just woken with eyes full of lacrilube so I'm going to save them for later but very excited about this latest research - even if, as you point out, it's in its infancy. If evidence backs it up then I just hope it feeds into neurological practice soon. Tx

  • Cheers, nomoreheels :) I don't much like medicalxpress's style, which is often full of hyperbole and bias. Phrases like 'stunning discovery' and 'The impossible existed' have no place in science writing, if you ask me! But one good trick is to take the researchers' names and a few keywords from a medx article and google them to find a less over-excited report on the same subject!

  • Hi Guys I am glad that you found the post interesting and I have enjoyed the comments so far.

  • It is more than interesting Liberton - it looks like a really promising breakthrough might be in the way and I'm really grateful to you for drawing it to our attention.

    As someone who suffers more presently from neuro symptoms than from RA, despite being diagnosed with RA five years ago, I'm intrigued because my MS-like symptoms are still not accounted for and this could explain why.

    Here's another link that might be of interest to many of you because it highlights the neurological aspect to some with connective tissue diseases - specifically Sjogrens - which often overlaps with RA and Lupus.

    hopkinssjogrens.org/disease...

    There are a few typos in it but generally speaking I think it's very sound and well laid out and reading it has helped me a great deal.

  • Wonderful link Twitchy!!!

    I am undergoing tests at the moment to try to work out whether I have MS as well as Sjogrens! Having read that , it seems extremely complex and I think Sjogrens seems to be at the root of many of my weird symptoms as well perhaps of yours. X

  • Yes I thought of you and meant to PM it to you Cutty. Interestingly someone on NeuroTalk PM forum says that the chap who wrote it is their rheumy and he "saved their life"! I'd do a great deal for a rheumy like this but I don't think moving to the States is an option I would plump for!

    The part about SSJ being misdiagnosed as MS is particularly interesting. Since my lumbar puncture over a year ago this has been ruled out for me but I do have these paired Oligoclonal bands and Sjogrens is one of the diseases that flags up with these bands.

    I don't know how I will ever find a rheumy who is prepared to get beyond the lack of positive antibodies as you have done - but moving to the larger teaching hospital across the water is my current thinking.

    Interestingly my rheumy was one of a few recommended by the British Sjogrens Syndrome Assiciation as being a doctor with a special interest in SSJ. Not for me so far!

    I also observe that in this article he says that those with a neurological type of Sjogrens are often the people who don't have the positive antibodies. I'm almost sure this is me and that my non erosive RA is secondary to primary Sjogrens. I've been dry all my life - and I don't just mean my sense of humour or preference for non alcholic beverage!

    But as my teeth aren't bad and my mouth isn't that dry no one will commit to a diagnosis of SSJ or risk the lip biopsy. My lips are always tingly and numb anyhow these days because of the SFN so I may push for it because it would be great to have a name to pin my symptoms to at last rather than idiopathic small fibre neuropathy!

    And my eyes, nose and the rest are all terribly dry and I no longer produce sweat so I think what little moisture I have must all reside in my mouth!

    Glad you've got the link before your MS tests - maybe worth printing it off and showing to your neuro or rheumy - especially with the new Virginia uni research being in everyone's minds? X

  • Good to hear your thoughts on it Twitchy but sorry you are no nearer yet to the elusive answers.

    I actually had a lip biopsy fifteen years ago and it was negative, but the doctor who asked for it (a pancreatic surgeon) discounted that ,and just said it had not infiltrated that area yet!!!!

    He was still certain it was Sjogrens. I think also it depends on which nodes in the lip are targeted for evaluation. Goodness knows, but my present Rheumy still thinks Sjogrens but I don't want a repeat lip biopsy.

    I have had a bad attack of optic neuritis recently along with other weird neuro things hence they are hunting again for MS.

    I had an Evoked Visual Potential test last week and maybe another MRI coming up soon. The last one was three years ago.

    So it goes on!!

    Hope you have managed to find another letting house meantime!

    C xx

  • How stressful it is to have another disease hanging over you Cutty. I'd never have another lumbar puncture done even for clarity - and I believe this is the most definitive test for MS - my brain MRI was okay. So I may have to try to resign myself to never knowing.

    But re the potential discovery this post refers to - an oral surgeon (these type of HCPs seem to be my heros!) explained that there are nerves running up the back of our skulls which are much less commonly checked for lesions and ganglions. I've asked about this but his promised letter never materialised so my last neurologist was baffled. Hoping the new one can shed more light - particular with this new research revealing that there may be other, previously undiscovered routes for the immune system to transmit to and from the brain now. hope it's not just another case of "is there or isn't

    there life on Mars?" though! Tx

  • I do think we are on the brink of many interesting discoveries re immunology and the brain etc .

    Trouble is we want answers now!!

    I want quality of life now, not when I am much much older than my present 62!

    Maybe I will have a new lease of life at 82 and have the best bits of my life yet to live!!

    My Mum's side has extremely long living genes despite any health problems they all had and they were many! But goodness knows which side I have got!

    I know you are not favourably blessed Twitchy in that department, but on the brighter side your Mum and Dad were never diagnosed nor treated,so had years of their health problems secretly cooking up problems for them.

    And this year Twitchy they are going to crack it for you!!!

    I have a feeling those medics across the water will give you a more helpful reappraisal . I have heard many good things about that hospital.

    Have also heard of another excellent Rheumy, not near us but will send you a pm about it.

    But first large filling at the dentist this morning!!

    C xx

  • Okay good luck with the filling. You need my numb gums to deal with this I think!

    At least you do have doctors who take your problems seriously and continue to investigate. I hope you're right about going across the water. I've just got to be diplomatic about it all and I'm told the paired Oligloclonal bands in my CSF are key to making progress and I should ask to see an immunologist about them. How I go about doing this I'm not entirely sure yet. X

  • It would explain a lot I think! Many of my symptoms are interlinked and I hope they can continue their research .

    Interestingly I saw a news piece yesterday saying that there is a possibility we can have neuro statins in the future ( like cholesterol stains ) but to avoid dementia. Neither my " brain fog" it made me sit up and listen!

    That would be so helpful if the research is correct!!thanks for this info .

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