Sunday, 8 October 2017

Brain Drain Pipes: A waste removal system or the immune activating pathway

As you know I have been moaning about the Late Breaking abstracts selection at ECTRIMS2017, yep sour grapes:-(...as our paper wasn't selected for a talk:-(  

We will report on how and why cladribine works 

Luckily (for them) our cladribine poster on effects on lymphocytes is not next to the company sponsored poster. Wonder what they will say?  But as my alemtuzumab poster in next to it, I'll get hear:-).

But as for the rest of the late breakers we have many where the results are announced, so if you are pressed for time you can get home early.

1. We have the Fingolimod trial in children.....It worked (CLICK HERE)

2. We have anti retro virus trial...It failed at 6 months (CLICK HERE) but then it worked at 6 months (CLICK HERE)


3. The ozanimod (Fingolimod me-too) trial.... It worked (CLICK  HERE)
4. Are neurofilaments a biomarker for trials? My guess is Yes
5. We have pathogenic antibodies to MOG, which we are not sure if this is that important to all or only a subset of MS
6. Looking forward to the MS sprint progressive trial but no announcement from Medicinova...except that enrollment was completed in Sept and results expected 2018 (CLICK). But then they say "Dr. Fox will present the top line safety, tolerability and efficacy data of ibudilast in progressive MS".
7. Then there was the last one imaging lymphatics in primates, I thought who is interested in monkey brains?

Anyway we don't have to wait for ECTRIMS and glad to see that humans are imaged and so it is clear we have drainpipes from the brain. These will take stuff into the lymph glands.

Absinta M, Ha SK, Nair G, Sati P, Luciano NJ, Palisoc M, Louveau A, Zaghloul KA, Pittaluga S, Kipnis J, Reich DS. Human and nonhuman primate meninges harbor lymphatic vessels that can be visualized noninvasively by MRI. Elife. 2017 Oct 3;6. pii: e29738. doi: 10.7554/eLife.29738
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Here, we report the existence of meningeal lymphatic vessels in human and nonhuman primates (common marmoset monkeys) and the feasibility of noninvasively imaging and mapping them in vivo with high-resolution, clinical MRI. On T2-FLAIR and T1-weighted black-blood imaging, lymphatic vessels enhance with gadobutrol, a gadolinium-based contrast agent with high propensity to extravasate across a permeable capillary endothelial barrier, but not with gadofosveset, a blood-pool contrast agent (Gadofosveset binds reversibly to serum albumin, increasing its molecular weight from 0.9 to 67 kDa. Under physiological conditions, albumin has a low transcapillary exchange rate into the interstitial compartment, estimated to be on the order of 5% per hour, which explains the propensity of gadofosveset to remain within blood vessels). The topography of these vessels, running alongside dural venous sinuses, recapitulates the meningeal lymphatic system of rodents. In primates, meningeal lymphatics display a typical panel of lymphatic endothelial markers by immunohistochemistry. This discovery holds promise for better understanding the normal physiology of lymphatic drainage from the central nervous system and potential aberrations in neurological diseases.
So we know that there is lymphatic type drainage in rodents and the presence of glymphatics and not it is evident that there are drainage pathways from the brain. It means that proteins can move from the brain to the node.
If you are interested in reading the brain drainage system has been known for some time, so you can even read about the glymphatics

However in the study they could not prove whether lymphatic vessels drain immune cells, CSF, or other substances from the brain to deep cervical lymph nodes, nor could we assess any link with the glymphatic system
There is a neat video if you follow the link to the paper, so the next question is where does the spinal cord drain to? I suppose I can ask this at ECTRIMS2017 in a couple of weeks
    The lymphatics  of the human brain

3 comments:

  1. Could apoptosis related problems / impairment in this mechanism (like in lupus) be found there? I guess this is something to check...

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  2. How do you think a blocked glymphatic system would effect the brain MD? How does this relate to MS or other neurodegenerative disorders? Doesn't all lymphatics eventually drain into veins?

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    Replies
    1. I don't know that they block. The lymphatics drain into lymph glands and do eventually go into blood

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