Inhibiting blood to save the brain

March 22, 2007

A fibrous protein called fibrinogen, found in circulating blood and important in blood clotting, can promote multiple sclerosis (MS) 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.

"Current strategies to develop therapies to fight MS primarily target T cells," said Katerina Akassoglou, Ph.D., assistant professor in UCSD's Department of Pharmacology, whose study was published in the March 19 issue of Journal of Experimental Medicine. "Blood proteins have been neglected as a therapeutic target, but this research shows that a blood clotting factor is an important player in MS."

MS is an inflammatory disease that affects the central nervous system, causing symptoms such as loss of balance and muscle coordination, and changes in cognitive function. The disease is marked by loss of myelin, a material that coats nerve fibers. Past studies showed that the destruction of the myelin sheath is associated with the accumulation of fibrinogen deposits in the brain of human MS patients. In this study, Akassoglou and colleagues showed that fibrinogen is not merely associated with the damage in MS, but an active participant. Fibrinogen activates macrophage cells in the brain called microglia, causing inflammation which damages myelin.

The scientists sought to design a therapeutic strategy that would block the damaging effects of fibrinogen without affecting its beneficial blood coagulation. Studying a mouse model, the researchers identified a specific receptor called Mac-1 that is expressed by microglial cells and binds to fibrinogen. Mice expressing a mutant form of fibrinogen that failed to bind Mac-1 had fewer inflammatory lesions and less severe MS symptoms. Blocking the interaction between Mac-1 and fibrinogen after the first episode of paralysis using the fibrin peptide prevented subsequent relapses. It also prevented further microglia activation and damage to myelin in the diseased mice, allowing them to survive with improved motor function.

"Importantly, this approach blocks fibrin's interaction with microglia, but not with platelets, so clotting wouldn't be impacted," said Akassoglou, adding that this potential MS therapy might also have applications to other blood-brain barrier diseases where blood leakage and microglia activation is present such as spinal cord injury, Alzheimer's disease or stroke.

Source: University of California - San Diego

Explore further: Researchers show possible trigger for MS nerve damage

Related Stories

Researchers show possible trigger for MS nerve damage

November 27, 2012

High-resolution real-time images show in mice how nerves may be damaged during the earliest stages of multiple sclerosis. The results suggest that the critical step happens when fibrinogen, a blood-clotting protein, leaks ...

Blood clotting protein triggers immune attack on the brain

October 9, 2015

A new study from the Gladstone Institutes shows that a single drop of blood in the brain is sufficient to activate an autoimmune response akin to multiple sclerosis (MS). This is the first demonstration that introduction ...

Recommended for you

Artificial beta cells

December 8, 2016

Researchers led by ETH Professor Martin Fussenegger at the Department of Biosystems Science and Engineering (D-BSSE) in Basel have produced artificial beta cells using a straightforward engineering approach.

Key regulator of bone development identified

December 8, 2016

Loss of a key protein leads to defects in skeletal development including reduced bone density and a shortening of the fingers and toes—a condition known as brachydactyly. The discovery was made by researchers at Penn State ...

Researchers question lifelong immunity to toxoplasmosis

December 8, 2016

Medical students are taught that once infected with Toxoplasma gondii—the "cat parasite"—then you're protected from reinfection for the rest of your life. This dogma should be questioned, argue researchers in an Opinion ...

TET proteins drive early neurogenesis

December 7, 2016

The fate of stem cells is determined by series of choices that sequentially narrow their available options until stem cells' offspring have found their station and purpose in the body. Their decisions are guided in part by ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.