Nov. 27, 2012 10:17 AM
NIH researchers find that fibrinogen appears to be "the trigger" which begins neurodegeneration in MS.
Researchers are honing in on fibrinogen as a mediator in vascular disease, and they are also finding a link in MS.
Fibrinogen is always present in the blood. The normal range is 200 - 400 milligrams per deciliter (mg/dL).
Fibrinogen is a protein which is made in our livers. It's the signaling protein for fibrin, which allows our blood to clot. When people develop venous ulcers on their legs, due to chronic venous insufficiency, it's fibrinogen that leaks from the veins and creates a build up of fibrin, depleting the tissue of oxygen and allowing those hallmark ulcers to form. This is called a "fibrin cuff." It's fibrinogen which initiates the coagulation cascade and causes our blood to thicken, as a response to low oxygen levels.
Dr. Zamboni was the first to suggest that MS lesions looked a lot like venous ulcers because of the fibrin cuffs found in both sites of injury.
And researchers have noted that fibin deposition comes FIRST, before demyelination.
Here is some recent research on this connection:
Compromised vasculature in the nervous tissue is a pathogenic manifestation apparent in traumatic injuries, such as spinal cord, optic nerve, and sciatic nerve injury, as well as in central nervous system (CNS) diseases with autoimmune characteristics, such as multiple sclerosis (MS) (7).
Blood-brain barrier (BBB) disruption precedes clinical symptoms in MS patients (8), and fibrin is deposited in the lesions (9, 10), apparently before cerebral tissue injury and demyelination (11). Fibrin deposition also coincides with areas of demyelination (12), as well as with areas of axonal damage.
This finding, in accord with the earlier literature [2], suggests the presence of a procoagulant state in MS, and elements of the coagulation system such as fibrin and tissue factor (TF) are found in MS lesions
In particular, a proinflammatory role for fibrinogen has been reported in vascular wall disease, stroke, spinal cord injury, brain trauma, multiple sclerosis, Alzheimer's disease, rheumatoid arthritis, bacterial infection, colitis, lung and kidney fibrosis, Duchenne muscular dystrophy, and several types of cancer.
A fibrous protein called fibrinogen, found in circulating blood and important in blood clotting, can promote multiple sclerosis when it leaks from the blood into the brain, triggering inflammation that leads to MS-related nerve damage. Researchers at the University of California, San Diego (UCSD) School of Medicine have identified a fibrin-derived peptide that inhibits this specific inflammation process in mouse models of MS, reducing MS symptoms.
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Dr. J. Stephen Alexander is an endothelial researcher at LSU. He will be presenting at the next ISNVD conference, in Orlando in February. I met Dr. Alexander in Bologna in 2009 at the first CCSVI conference and we discussed the blood connection in MS. Dr. Alexander co-authored a paper on platelet abnormalities in MS in 2008.
Our observation of platelet abnormalities in MS [6] and subsequent observation of thrombosis in cutaneous venules and capillaries adjacent to subcutaneous ulcers complicating subcutaneous injections of interferon-beta1b [7] heightened our interest in a possible role of platelet dysfunction in MS.
Here is his paper from 2006, Looking at MS as a Vascular Disease-
Here we focus on MS as a vascular disease. The reason for such an explicit manuscript is to clearly show the role of cerebral endothelial cells as the doorway for trafficking inflammatory cells to provoke the flood of cytokine and chemokines within the CNS. The concept of endothelial dysfunction in MS is not new but is certainly under-investigated. We hope to share our inclination that endothelial cells are key elements in MS pathogenesis and consequently to promote vascular targeting as the next frontier for the treatment of this incurable condition.
How can people with MS address these higher levels of fibrin? Exercise, quitting smoking, stress reduction, low fat diets and fresh fruits and vegetables--all can lower fibrinogen levels. And knowing your serum numbers and having them tested regularly is essential, especially before and after venoplasty. Please see this article I wrote up with Al Ossario for CCSVI Alliance--it goes through all of the blood tests for coagulation numbers-
I also hope researchers will take serum levels while pwMS are in the midst of an exacerbation. Waiting to take serum levels during remission doesn’t help. By then, the coagulation cascade may have ceased, and serum numbers may return to normal. But during an acute flare, these blood numbers can be noted.
I hope these thoughts might be of help to you, as you search for answers in your own MS process, and maintaining flow.
Joan
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