• Welcome to Phoenix Rising!

    Created in 2008, Phoenix Rising is the largest and oldest forum dedicated to furthering the understanding of and finding treatments for complex chronic illnesses such as chronic fatigue syndrome (ME/CFS), fibromyalgia (FM), long COVID, postural orthostatic tachycardia syndrome (POTS), mast cell activation syndrome (MCAS), and allied diseases.

    To become a member, simply click the Register button at the top right.

Missing link found between brain, immune system -- with major disease implications

Jonathan Edwards

"Gibberish"
Messages
5,256
Still struggling a bit to work out exactly what these people have found. The report talks of lymphatics where sinuses lie in dura but I wonder if they know what the entry point is like? Thinking about it one might expect there to be continuity with lymphatic vascular structures penetrating into brain tissue along the path of the exiting vein and these might be to some extent compartmentalised off from free CSF. There might even be one cell thick vessels penetrating throughout brain substance. But then there is the question of why you would have these AND 'glymphatic' channels of freely mobile CSF. Or are the glymphatics really the lymphatics after all. In which case it seems likely that the CSF in them is at least partially separate from the bulk pool - maybe completely separate in terms of convective and cellular movement.
 

anciendaze

Senior Member
Messages
1,841
I am not quite sure what point you are wanting to make anciendaze. We all agree that movement of cells across vessels is quite different from fluid and solute flux. I was not suggesting that there was any relevance of one to the other. And clearly intravasation has a different mechanism from extravasation, as I thought I had implied. So lymphatic endothelium has different properties and surface molecules from blood vessels. I think we are still left with the question of how a dendritic cell in the thalamus might find its way to a dural lymphatic a few inches away and if it does do that in what way that makes things different from finding an arachnoid granulation to creep out of and into tissue lymphatics that way. I am not sure what the point of disagreement was to be honest!!
Not arguing that there is no problem left to research, quite the contrary. The problem with vascularization of the brain is bad enough when you are asking how supplies of oxygenated blood and glucose reach individual cells, and nobody is seriously questioning those vascular systems.

(Another line of inquiry I keep trying to open is about the effect of repeated transient episodes of hypoperfusion. This is significant in terms of repeated hypoxia alone, as is known in the case of mountain climbers going to extreme altitudes. What happens to immune response during hypoperfusion is a larger question.)

What has bothered me about prior explanations for immunology of the brain is that they didn't really form a system of any kind. Too much reminds me of the Sidney Harris cartoon with the blackboard including a step saying "then a miracle occurs". A great deal of published knowledge on these subjects falls in the category I call "stamp collecting". Some publications could be described as "not even wrong" or "word games". This new finding looks like the beginning of an avenue toward functional understanding.

As my separate comment in the same post concerning meningitis and the destination of this lymphatic system indicated, I am very glad we now have some explanation for a connection between deep cervical lymph nodes and the meninges or dura. I do not expect the story to be simple from there going deeper into the brain (nothing else is) but this is an encouraging start. What I do expect is that studies of leukocytes found within this system will tell us a great deal about immunological activity within the brain that we have been trying and failing to deduce from studies based on such things as leukocytes found in peripheral blood or findings at autopsy.

Elsewhere I've said that published reports of pituitary hypophysitis caused by leukocyte infiltration suggest incidence of this is somewhere between 1 in 40 and 1 in 10,000,000 of the general population. This is tantamount to saying we don't have the foggiest idea about immune behavior right at the base of the brain. This is very relevant to disturbances of the HPA axis.

I first became aware of this when one study of 10 living veterans with GWI found 8 cases of hypophysitis based on high-resolution scans, about the total number of cases for a year from the entire U.K. population. This then devolved into the usual arguments about thresholds for diagnosis and statistical anomalies. Since then I've been trying to find out what anyone actually knows about this fairly well defined problem. The answer seems to be "not much".
 

Marco

Grrrrrrr!
Messages
2,386
Location
Near Cognac, France
I find it hard to envisage very major back and forth convective fluid flow in big lumps of deep brain like internal capsule and thalamus but it sounds as if there is at least some convetive exchange to be expected. That will speed up the diffusional model I was working with but probably does not alter the overall structure of the dynamics.

I like it. Maybe analagous to how ocean current supply a steady flow of nutrients to filter feeders on coral reefs? Extrapolating on from a hypothesis I wonder if this ancillary flow might help the diffusion model deal with local concentrations (of metabolites/proteins?) by spreading the load?

I also found it interesting that this glymphatic system is more active during sleep which is a nice relaxing idea that gentle currents waft through the brain helping to clear away all the accumulated debris from a hard day. As the theory suggests and as I'm sure we've discusssed here previously, what happens when sleep is disrupted?
 

Jonathan Edwards

"Gibberish"
Messages
5,256
I like it. Maybe analagous to how ocean current supply a steady flow of nutrients to filter feeders on coral reefs? Extrapolating on from a hypothesis I wonder if this ancillary flow might help the diffusion model deal with local concentrations (of metabolites/proteins?) by spreading the load?

I also found it interesting that this glymphatic system is more active during sleep which is a nice relaxing idea that gentle currents waft through the brain helping to clear away all the accumulated debris from a hard day. As the theory suggests and as I'm sure we've discusssed here previously, what happens when sleep is disrupted?

And why do I get nightmares? Not that I get them too often mind. Maybe its the brain beating its doormat to get all the rubbish out before breakfast.
 

MeSci

ME/CFS since 1995; activity level 6?
Messages
8,231
Location
Cornwall, UK
I always knew Reggie's brother was an osteopath - sort of felt it in my bones - or in my waters maybe.
Better (but less funny) than Doc Morrissey, presumably.
Doc Morrissey: Do you find you can't finish the crossword like you used to, nasty taste in the mouth in the mornings, can't stop thinking about sex, can't start doing anything about sex, wake up with a sweat in the mornings, keep falling asleep during '"Play For Today"?

Reginald Perrin: That's extraordinary, Doc! That's exactly how I've been feeling.

Doc Morrissey: So have I. I wonder what it is? Take two aspirins.

:lol:
 
Last edited:

MeSci

ME/CFS since 1995; activity level 6?
Messages
8,231
Location
Cornwall, UK
First we learnt about retrovirology for xmrv; then a beginner's course in medical stats for the PACE trial, and a crash course in study design and good practice for medical trials; then a crash course in autoimmunity for rituximab; then it was the krebs cycle and metabolism for Julia Newton's research; and now it looks like it will have to be an anatomy lesson as well! Oh, and then there's genetics, epigenetics, and immunology. With a little oncology thrown in, and proteomics and metabolomics yet to come. Have I missed anything? I've probably missed quite a bit. At least our illness won't have been a complete waste of time - if we don't all have enough knowledge to get a degree in biology by the time we're cured, then I'll be very surprised! :)

Edit: oh, and expert crowdfunders, bloggers, community support advisers, carers and advocates thrown in to the mix. Not to mention making lots of wonderful friends and meeting quality fellow travellers on the way.

Sorry, slightly off-topic!

I already have relevant degrees but am still learning a lot from PR. When I am tired or brain-fogged it is very beneficial to read other people's analyses of scientific papers, to help me to look at things in different ways and take in new ideas and new knowledge. Learning should never stop. I love it!
 

anciendaze

Senior Member
Messages
1,841
Just had another thought about implications of a lymphatic system with one side of vessels on the dura and the other on the surface of the meninges. This helps explain the sometimes bizarre effects and unpredictable progression of symptoms due to a subdural hematoma. Blood clots blocking lymphatic drainage in other parts of the body, like the liver, can result in nasty problems.

I even turned up a reference to an old paper puzzling over the latent interval between trauma and symptoms based on the "knowledge" that there was no such lymphatic system!

Added: this suggests there may be other problems caused by leaks of lymphatic fluid which would not be classified as hematomas. Localized accumulations of fluid should show up on some kinds of imaging, but are very likely to be ignored, based on current conventional medical wisdom. I think I've heard scattered reports of such things. Maybe somebody can supply a reference.
 
Last edited:
Messages
296
I haven't seen this video but I am familiar with Dr Morse and his teachings. I do not agree with his approach but I am surprised to find that he was speaking about this years ago.

 

lansbergen

Senior Member
Messages
2,512
And why do I get nightmares? Not that I get them too often mind. Maybe its the brain beating its doormat to get all the rubbish out before breakfast.

Nightmares were part of my improving process at a certain timepoint. It was during the time I slowy got my memorie back.
 

Sasha

Fine, thank you
Messages
17,863
Location
UK
Jarred Younger has posted about this (as I saw on MEA FB - I've broken up the paras for ease of reading).

Very interesting last few paras.

https://www.facebook.com/permalink....230465430&id=1543963919214695&hc_location=ufi

Jarred Younger said:
You may have seen this recent study about the discovery of lymphatic vessels in the brain. Many scientists are excited about the findings.

The lymphatic system is a series of valves, pumps, and immune cells involved in circulation and immune defense in the body.

Several studies have reported that individuals with ME/CFS have a higher incidence of swollen lymph nodes, suggesting an infection or immune dysfunction.

Until now, we thought that the lymphatic system existed only in the body, and not in the brain. The finding that the lymphatic system extends to the brain has huge implications for neuroinflammation, pain and fatigue.

It provides a logical pathway by which inflammation can travel to the brain, potentially leading to neurodegenerative conditions and other central nervous system disorders.

You can read more about the story with the link below. I read the original study – the researchers did a very meticulous job to ensure their conclusions were justified.

The observations were made almost solely in mice, but some very preliminary data were presented suggesting the findings hold true for humans as well.

If confirmed, there are at least two ways the findings would be important for our lab's work.

First, if the brain lymphatic system is connected to the body lymphatic system, we could extract and analyze the draining lymph to measure the inflammatory chemicals from the brain much more easily than drawing cerebrospinal fluid with a spinal tap.

Second, if we can develop a way to neuroimage the lymph nodes in the brain, we may be able to see swelling that can help us diagnose central inflammation.

We’ll be working on it!

- Jarred Younger
 

Scarecrow

Revolting Peasant
Messages
1,904
Location
Scotland
Thanks @Sasha. Interesting that Younger should pick up on this so quickly.

It provides a logical pathway by which inflammation can travel to the brain, potentially leading to neurodegenerative conditions and other central nervous system disorders.
I don't understand this statement. Can anyone help?
 

MeSci

ME/CFS since 1995; activity level 6?
Messages
8,231
Location
Cornwall, UK
Jarred Younger has posted about this (as I saw on MEA FB - I've broken up the paras for ease of reading).

Very interesting last few paras.

https://www.facebook.com/permalink....230465430&id=1543963919214695&hc_location=ufi

I hadn't realised that this finding was only in mice. I think I will wait until findings are confirmed in humans before I pay it any more attention, as I have found time and time again that non-human findings do not correlate with human findings. With time and energy limited, I can't afford to waste any!
 

roller

wiggle jiggle
Messages
775
the worse i feel, the more white pus (lymp?) i have in the navel.

once after sit-ups there was a huge 'flush' from my belly to the left leg.

once after taking an 80% ethanol with some herbs (melissa, valerian...similars) for the first time, i woke up and had a big water 'flushing' in the head. on the side i slept (right). this was scaring.

large amounts of some liquid.
 
Last edited: