gray matter / white matter connection

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gray matter / white matter connection

Postby dignan » Thu Apr 30, 2009 9:16 am

I really like that they are looking at a common target that exists in gray and white matter.

Gray matter under attack in multiple sclerosis

April 30th, 2009 -- It has long been assumed that myelin is the most important target for the misdirected immune response in MS. This white, fat-rich protective layer of specialized cells enshrouds the long extensions of neurons. However, the central nervous systems of MS patients also exhibit damage in the gray matter, where the nerve cell bodies are located. How the patient's disability develops depends greatly on the damage of the gray matter.

An international group headed by medical scientist Professor Edgar Meinl of LMU Munich has now discovered a possible connection: The protein Contactin-2 is produced both in the myelin sheathing and by neurons in the gray matter - and is attacked by misdirected immune factors. "Our results suggest that these processes also play a role in MS patients," says Meinl. "It could even be that proteins existing both in myelin and in the gray matter are in fact the critical points of attack."

Multiple sclerosis often advances in phases, where nerve fibers are successively and irreversibly destroyed by attacks from certain immune cells - so-called T-lymphocytes. The axons that make up nerve fibers are sheathed in myelin. This protective layer consists of individual cells that wrap around the long extensions of the neurons to insulate them and to allow signals to propagate all the way along the nerve cells. MS first causes in an irrecoverable loss of myelin, and then ultimately to the demise of the neurons thus exposed.

"It is the irreversible destruction of axons in particular that causes the lasting disability of patients," explains Professor Edgar Meinl of the Institute of Clinical Neuroimmunology at LMU Munich Klinikum and of the Max Planck Institute of Neurobiology. Little by little, damage spreads out in the brain and spinal cord. Different symptoms can follow, depending on where these lesions first appear and how severe they are. These could be loss of sight and speech, or tremors, numbness, impaired bladder function or impaired mobility.

It is only a recent discovery that the immune system actually attacks the gray matter in the early stages, along with the myelin sheathing. "This extensive damage is a factor in the advancement of the symptoms," says Meinl. "Until now, it has been unclear which molecules direct the immune system against the gray matter." The researchers therefore performed large-scale tests to investigate which proteins in human brain tissue the antibodies of MS patients dock onto, instead of docking onto foreign intruders as they are supposed to.

In the course of their investigations, they identified Contactin-2 as a new autoantigen - a molecular structure that belongs to the body but which provokes an immune response. This protein is found in the brain and spinal cord, and is present in both the myelin sheathing and in the neurons themselves - which means it exists in the gray matter. "Contactin-2 triggers an immune response in which T-cells and antibodies turn against this molecule," reports Meinl. "In some ways, this immune response is similar to those that occur in pathogen-induced inflammations."

In an animal model, autoresponsive T-cells responded to TAG-1, the animal protein analogous to human Contactin-2. The T-cells triggered an inflammation in the brain, predominantly in the gray matter. Furthermore, these immune cells also opened the blood-brain barrier, which is a barrier that most molecules and cells can normally not get past. "Without this barrier, the antibodies were able to invade the brain in great numbers, where they caused severe damage to the gray matter," says Meinl. "What we now need to clarify is whether these mechanisms also take place in human MS patients, and what role is played by antigens that occur inside the neurons."
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Postby 71jules » Thu May 07, 2009 12:39 am

Hi and I was very interested in reading your post.
I have posted a question about white matter and or grey matter as my MRI showed change in two areas on both sides of the brain in those areas.
No answer though as to why or what it is. My current posts on here are under PLEASE HELP I AM SO SCARED and RESULTS ARE IN AND I AM CONFUSED.
So many symptoms of MS but MRI didn't support the finding which I am relieved but very surprised.
I don't know whether to pursue this down the line with another MRI.
Thanks again.
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Postby cheerleader » Thu May 07, 2009 6:49 am

Thanks for that research, dig...
I'm also glad they're looking beyond the myelin, and seeing that this process involves the entire brain. The contactin 2 connection is interesting...contactin 2 is a brain protein that allows cells to communicate, the fact that it is found in all brain tissue would point to a complete assault on the entire brain- something we've been seeing with new technologies like 7Tesla.

Jules, you really need to ask these questions of a doctor. We are not qualified to read your MRI report. Hyperintensities are not the same as MS lesions. Take care, and talk to your doc today-
Husband dx RRMS 3/07
dx dual jugular vein stenosis (CCSVI) 4/09
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Postby 71jules » Thu May 07, 2009 11:03 pm

Hi cheerleader

Thanks for that and I didn't realise my post made it sound like I was asking people to read my MRI report.
I posted the results seeing if anybody had similar findings on any of their scans.
I am also just trying to work out whether a follow up MRI is worthy in this situation.
I was interested reading about the white/grey matter as that is the area that showed up as changed.

You take care too and thank you for the advice.

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