Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

NIH-funded researchers show possible trigger for MS nerve damage

28.11.2012
Results of study in mice may lead to new treatments

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 into the central nervous system and activates immune cells called microglia.


Microglia (green cells) cluster around leaking blood vessels days before neurological damage occurs in a mouse model of MS.

Credit: Courtesy of Akassoglou lab, Gladstone Institute

"We have shown that fibrinogen is the trigger," said Katerina Akassoglou, Ph.D., an associate investigator at the Gladstone Institute for Neurological Disease and professor of neurology at the University of California, San Francisco, and senior author of the paper published online in Nature Communications.

Multiple sclerosis, or MS, is thought to be an autoimmune disease in which cells that normally protect the body against infections attack nerve cells in the brain and spinal cord, often leading to problems with vision, muscle strength, balance and coordination, thinking and memory. Typically during MS, the immune cells destroy myelin, a protective sheath surrounding nerves, and eventually leading to nerve damage. The immune attack also causes leaks in the blood-brain barrier, which normally separates the brain from potentially harmful substances in the blood.

"Dr. Akassoglou has focused on the role of the blood-brain barrier leak in MS and has discovered that leakage of the blood clotting protein fibrinogen can trigger brain inflammation," said Ursula Utz, Ph.D., M.B.A., a program director at NIH's National Institute of Neurological Disorders and Stroke (NINDS).

Microglia are cells traditionally thought to control immunity in the nervous system. Previous studies suggested that leakage of fibrinogen activates microglia. In this study, Dr. Akassoglou and her colleagues used a cutting-edge imaging technique called two-photon laser scanning microscopy to watch what happens in an animal model of MS.

"Our results provide the first evidence linking leakage of fibrinogen to neuronal damage," said Dr. Akassoglou, "Vascular changes are the instigator of neurotoxicity."

Using a mouse model of MS, the researchers found that leakage of fibrinogen and microglial activation occurred days before nerve damage began, suggesting they occur in an early, pre-clinical stage of the disease.

During this period, microglia changed shapes and clustered around blood vessels along with other immune cells. Further experiments suggested that fibrinogen activated microglia by binding to a receptor, called CD11b/CD18, which caused the microglia to release reactive oxygen molecules that, in turn, damaged neurons. Inhibiting the binding of fibrinogen to the receptor prevented microglial activation and nerve damage.

Current treatments for MS are designed to suppress autoimmunity. The results from this study suggest that targeting the interaction between fibrinogen and microglia may be an effective alternative. In the mice, blocking fibrinogen's blood clotting activity prevented microglial activation and nerve damage.

"Current drugs target primarily downstream events. This interaction could be an upstream target that suppresses immunity and neurodegeneration," said Dr. Akassoglou.

In 2006, Dr. Akassoglou received a Presidential Early Career Award for Scientists and Engineers, which honors and supports the finest and most promising researchers early in their careers.

This study was supported by NINDS (NS051470, NS052189, NS066361); the National Cancer Institute (CA082103); the National Center for Research Resources (RR004050), the National Heart, Lung, and Blood Institute (HL096126), the American Heart Association, the Bechtel Foundation, the Dana Program in Brain and Immuno-imaging, the H. Lundbeck A/S, the Howard Hughes Medical Institute, the National Multiple Sclerosis Society, the Nancy Davis Foundation for Multiple Sclerosis, and the March of Dimes.

Reference: Davalos et al., "Fibrinogen-induced perivascular microglial clustering is required for the development of axonal damage in neuroinflammation." Nature Communications, published online November 27, 2012. DOI: 10.1038/ncomms2230

NINDS is the nation's leading funder of research on the brain and nervous system. The NINDS mission is to reduce the burden of neurological disease – a burden borne by every age group, by every segment of society, by people all over the world.

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.

Christopher Thomas | EurekAlert!
Further information:
http://www.nih.gov

More articles from Health and Medicine:

nachricht Fiber optic biosensor-integrated microfluidic chip to detect glucose levels
29.04.2016 | The Optical Society

nachricht Got good fat?
27.04.2016 | Rheinische Friedrich-Wilhelms-Universität Bonn

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Tiny microbots that can clean up water

Researchers from the Max Planck Institute Stuttgart have developed self-propelled tiny ‘microbots’ that can remove lead or organic pollution from contaminated water.

Working with colleagues in Barcelona and Singapore, Samuel Sánchez’s group used graphene oxide to make their microscale motors, which are able to adsorb lead...

Im Focus: ORNL researchers discover new state of water molecule

Neutron scattering and computational modeling have revealed unique and unexpected behavior of water molecules under extreme confinement that is unmatched by any known gas, liquid or solid states.

In a paper published in Physical Review Letters, researchers at the Department of Energy's Oak Ridge National Laboratory describe a new tunneling state of...

Im Focus: Bionic Lightweight Design researchers of the Alfred Wegener Institute at Hannover Messe 2016

Honeycomb structures as the basic building block for industrial applications presented using holo pyramid

Researchers of the Alfred Wegener Institute (AWI) will introduce their latest developments in the field of bionic lightweight design at Hannover Messe from 25...

Im Focus: New world record for fullerene-free polymer solar cells

Polymer solar cells can be even cheaper and more reliable thanks to a breakthrough by scientists at Linköping University and the Chinese Academy of Sciences (CAS). This work is about avoiding costly and unstable fullerenes.

Polymer solar cells can be even cheaper and more reliable thanks to a breakthrough by scientists at Linköping University and the Chinese Academy of Sciences...

Im Focus: Ultra-thin glass is up and coming

As one of the leading R&D partners in the development of surface technologies and organic electronics, the Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP will be exhibiting its recent achievements in vacuum coating of ultra-thin glass at SVC TechCon 2016 (Booth 846), taking place in Indianapolis / USA from May 9 – 13.

Fraunhofer FEP is an experienced partner for technological developments, known for testing the limits of new materials and for optimization of those materials...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

The “AC21 International Forum 2016” is About to Begin

27.04.2016 | Event News

Soft switching combines efficiency and improved electro-magnetic compatibility

15.04.2016 | Event News

Grid-Supportive Buildings Give Boost to Renewable Energy Integration

12.04.2016 | Event News

 
Latest News

Winds a quarter the speed of light spotted leaving mysterious binary systems

29.04.2016 | Physics and Astronomy

Fiber optic biosensor-integrated microfluidic chip to detect glucose levels

29.04.2016 | Health and Medicine

A cell senses its own curves: New research from the MBL Whitman Center

29.04.2016 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>