Inhibiting blood to save the brain

Mar 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: Growing a blood vessel in a week

add to favorites email to friend print save as pdf

Related Stories

Recommended for you

Growing a blood vessel in a week

Oct 24, 2014

The technology for creating new tissues from stem cells has taken a giant leap forward. Three tablespoons of blood are all that is needed to grow a brand new blood vessel in just seven days. This is shown ...

Testing time for stem cells

Oct 24, 2014

DefiniGEN is one of the first commercial opportunities to arise from Cambridge's expertise in stem cell research. Here, we look at some of the fundamental research that enables it to supply liver and pancreatic ...

Team finds key signaling pathway in cause of preeclampsia

Oct 23, 2014

A team of researchers led by a Wayne State University School of Medicine associate professor of obstetrics and gynecology has published findings that provide novel insight into the cause of preeclampsia, the leading cause ...

Rapid test to diagnose severe sepsis

Oct 23, 2014

A new test, developed by University of British Columbia researchers, could help physicians predict within an hour if a patient will develop severe sepsis so they can begin treatment immediately.

User comments : 0