Messing about with suspected blocked blood vessels led to the CCSVI movement, that was discredited by science,
So yesterday we had the media suggesting that you should block a different vessel in the brain to get rid of MS.
One of the readers asked whether this is the beginning of CCSVI2
It was claimed that a “Team identifies brain’s lymphatic vessels as new avenue to treat
multiple sclerosis” in the headline from Medical express…”
What do they actually say?
Louveau A, Herz J, Alme MN, Salvador AF, Dong MQ, Viar KE, Herod SG, Knopp J, Setliff JC, Lupi AL, Da Mesquita S, Frost EL, Gaultier A, Harris TH, Cao R, Hu S, Lukens JR, Smirnov I, Overall CC, Oliver G, Kipnis J. CNS lymphatic drainage and neuroinflammation are regulated by meningeal lymphatic vasculature. Nat Neurosci. 2018. doi: 10.1038/s41593-018-0227-9. [Epub ahead of print]
Neuroinflammatory diseases, such as multiple sclerosis, are characterized by invasion of the brain by autoreactive T cells. The mechanism for how T cells acquire their encephalitogenic phenotype and trigger disease remains, however, unclear. The existence of lymphatic vessels in the meninges indicates a relevant link between the CNS and peripheral immune system, perhaps affecting autoimmunity. Here, we demonstrate that meningeal lymphatics fulfill two critical criteria: they assist in the drainage of cerebrospinal fluid components and enable immune cells to enter draining lymph nodes in a CCR7-dependent manner. Unlike other tissues, meningeal lymphatic endothelial cells do not undergo expansion during inflammation, and they express a unique transcriptional signature. Notably, the ablation of meningeal lymphatics diminishes pathology and reduces the inflammatory response of brain-reactive T cells during an animal model of multiple sclerosis. Our findings demonstrate that meningeal lymphatics govern inflammatory processes and immune surveillance of the CNS and pose a valuable target for therapeutic intervention.
This study, elegantly shows that there are drainage pathways from the brain to the lymph glands that may
remove stuff in the fluid bathing the brain and spinal cord.
This provides a methods of waste disposal system for the brain, allowing it to remove stuff it doesn’t want and allows the immune system to sense, what is occuring in the brain.
They also show that cells in the brain leave the brain via this route
and use a chemokine receptor (CCR7) that lymphocytes use to leave lymph
We know that cells rapidly disappear from lesions in EAE. This
provides a route.
We know that cells that leave the lymph glands can re-enter the blood
via a place called the thoracic duct.
It is suggested that there is something in the fluid that
calls lymphocytes into the CNS.
We know that nerve proteins are broken down and so they will enter the lymph glands this way.
The proteins will be taken up by macrophages/dendritic cells in the lymph glands and
they can stimulate white blood cells. Also the first few cells (which go in to the brain un-noticed becuase of their low number) entering the CNS may signal the recruitment of a major wave of cells that are noticed as clinical signs develop.
What is the signal? More research needed, but this could be any of a number of
inflammatory signals and is unlikely to anything new as biology would not need
to make a specific migratory signal.
The lymphocytes enter the
blood system and when they come across markers on the blood vessels (chemokines
and adhesion moleculets etc, triggered by early lesional events) that say “infection near me”, the immune
cells will pour in, do their business and then either die or leave.
So this is nice science but what does it mean to you.
According to the media, “It’s a new avenue to treatment”.
Indeed in the study they blocked the lymphatic vessels and less severe EAE developed.
They cut the nasal (i.n.) and menigeal (i.c.m) lymphatics with a molecular knife (visudyne & laser) to see what happens and the number of T cells exiting the brain into the lymph glands were reduced and also the development of EAE was delayed.
However, note this was just delayed by a few days and essentially all animals eventually got disease and one suspects that there would have been very little difference if the experiment had not been stopped at 20 days when animals are still getting worse disease (as the blue line was still on the way up).
Indeed, this is what you may have suspected as physical removal of the lymph gland does not stop neurological disease either, as shown by DrLove and colleagues in the Netherlands many years ago.
van Zwam M et al. Surgical excision of CNS-draining lymph nodes reduces relapse severity in chronic-relapsing experimental autoimmune encephalomyelitis. J Pathol. 2009; 217:543
Therefore, this is not a magic answer and sloppy media reporting to suggest this (again, although perhaps fuellted by the researchers in their media quotes) .
The lymphatics are there for a reason, like clearing out the brain-garbage (non-needed, nerve synapses) that accumulates each day and are then forgotten as we sleep. Therefore, we can remember new things the following day.
So if you think about finding some crack-pot doctor who would ever think of
doing something like severing the lymphatic pathways (which is highly unlikely)…Don’t do it…or in Dutch…Schtop 🙂