This Is MS Multiple Sclerosis Knowledge & Support Community

A protein involved in blood clotting may be a new indicator to help detect multiple sclerosis (MS) lesions before symptoms arise. The presence of the clotting protein, thrombin, signals an early stage of the disease when the blood-brain barrier is breached and the brain’s immune response is set into motion. The research was presented at Neuroscience 2013, the annual meeting of the Society for Neuroscience and the world’s largest source of emerging news about brain science and health. 30,000 scientists are attending this meeting. “Our research shows this indicator is a promising approach for detecting MS-like lesions early, even before major symptoms appear,” said senior author Katerina Akassoglou, Ph.D., of the Gladstone Institutes and the University of California, San Francisco. “Such sensitive indicators could act as red flags that signal neuroinflammatory changes in the brain not only in MS, but also in other diseases such as Alzheimer’s.” MS is a debilitating disorder that can be intermittent or progressive, and causes numbness, fatigue, difficulty walking, paralysis, and loss of vision in 2 million people worldwide. MS arises when the body’s immune system attacks its own myelin sheaths, the protective coverings that surround neurons and allow signals to move from one cell to the next. The researchers found that thrombin, usually a beneficial protein involved in blood clotting, builds up in the central nervous system as MS progresses. Thrombin enters in the brain together with fibrinogen, another clotting protein when the protective barrier between the blood and brain becomes leaky. Thrombin converts the fibrinogen to fibrin which activates brain’s immune cells that break down the protective myelin sheath that surrounds neurons in the central nervous system. Because thrombin levels increase as the disease progresses, the researchers conclude that it could be used as an early detector of the disease. In their studies, the researchers used a mouse model and demonstrated that MS symptoms increased as thrombin levels rose. Early detection of MS could result in more successful treatment of the disease. Research was supported with funds from the National Multiple Sclerosis Society, the Nancy Davis Foundation for Multiple Sclerosis, and the National Institutes of Health. Dr. Akassoglou outlined her findings in a press conference held on Sunday, November 10, and this summary was distributed with the press release. The scientific presentation of Dr. Akassoglou’s work will be delivered on Monday, Novermber 11. Neuroscience 2013 continues through Wednesday, November 13.

The researchers found that thrombin, usually a beneficial protein involved in blood clotting, builds up in the central nervous system as MS progresses. Thrombin enters in the brain together with fibrinogen, another clotting protein when the protective barrier between the blood and brain becomes leaky. Thrombin converts the fibrinogen to fibrin which activates brain’s immune cells that break down the protective myelin sheath that surrounds neurons in the central nervous system.

Here we show that the blood protein fibrinogen induces rapid microglial responses toward the vasculature and is required for axonal damage in neuroinflammation. Using in vivo two-photon microscopy, we demonstrate that microglia form perivascular clusters before myelin loss or paralysis onset and that, of the plasma proteins, fibrinogen specifically induces rapid and sustained microglial responses in vivo. Fibrinogen leakage correlates with areas of axonal damage and induces reactive oxygen species release in microglia. Blocking fibrin formation with anticoagulant treatment or genetically eliminating the fibrinogen binding motif recognized by the microglial integrin receptor CD11b/CD18 inhibits perivascular microglial clustering and axonal damage. Thus, early and progressive perivascular microglial clustering triggered by fibrinogen leakage upon blood-brain barrier disruption contributes to axonal damage in neuroinflammatory disease.

The involvement of the clotting cascade seems to be a fruitful avenue of inquiry. I think the evidence against autoimmunity (whatever that is) is inescapable. It seems it is becoming widely recognized that these clotting chemicals are more important than T or B cells which are only involved much later on. There is no mistaken recognition of self as an invader, rather some normally benign clotting agents cross a breach in the BBB, resulting in inflammation and the involvement of the immune system.