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 Nanotubes are beacons in cancer-imaging technique
23.05.2016 | Rice University

nachricht More light on cancer
20.05.2016 | Lomonosov Moscow State University

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: Worldwide Success of Tyrolean Wastewater Treatment Technology

A biological and energy-efficient process, developed and patented by the University of Innsbruck, converts nitrogen compounds in wastewater treatment facilities into harmless atmospheric nitrogen gas. This innovative technology is now being refined and marketed jointly with the United States’ DC Water and Sewer Authority (DC Water). The largest DEMON®-system in a wastewater treatment plant is currently being built in Washington, DC.

The DEMON®-system was developed and patented by the University of Innsbruck 11 years ago. Today this successful technology has been implemented in about 70...

Im Focus: Computational high-throughput screening finds hard magnets containing less rare earth elements

Permanent magnets are very important for technologies of the future like electromobility and renewable energy, and rare earth elements (REE) are necessary for their manufacture. The Fraunhofer Institute for Mechanics of Materials IWM in Freiburg, Germany, has now succeeded in identifying promising approaches and materials for new permanent magnets through use of an in-house simulation process based on high-throughput screening (HTS). The team was able to improve magnetic properties this way and at the same time replaced REE with elements that are less expensive and readily available. The results were published in the online technical journal “Scientific Reports”.

The starting point for IWM researchers Wolfgang Körner, Georg Krugel, and Christian Elsässer was a neodymium-iron-nitrogen compound based on a type of...

Im Focus: Atomic precision: technologies for the next-but-one generation of microchips

In the Beyond EUV project, the Fraunhofer Institutes for Laser Technology ILT in Aachen and for Applied Optics and Precision Engineering IOF in Jena are developing key technologies for the manufacture of a new generation of microchips using EUV radiation at a wavelength of 6.7 nm. The resulting structures are barely thicker than single atoms, and they make it possible to produce extremely integrated circuits for such items as wearables or mind-controlled prosthetic limbs.

In 1965 Gordon Moore formulated the law that came to be named after him, which states that the complexity of integrated circuits doubles every one to two...

Im Focus: Researchers demonstrate size quantization of Dirac fermions in graphene

Characterization of high-quality material reveals important details relevant to next generation nanoelectronic devices

Quantum mechanics is the field of physics governing the behavior of things on atomic scales, where things work very differently from our everyday world.

Im Focus: Graphene: A quantum of current

When current comes in discrete packages: Viennese scientists unravel the quantum properties of the carbon material graphene

In 2010 the Nobel Prize in physics was awarded for the discovery of the exceptional material graphene, which consists of a single layer of carbon atoms...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Networking 4.0: International Laser Technology Congress AKL’16 Shows New Ways of Cooperations

24.05.2016 | Event News

Challenges of rural labor markets

20.05.2016 | Event News

International expert meeting “Health Business Connect” in France

19.05.2016 | Event News

 
Latest News

Fast, stretchy circuits could yield new wave of wearable electronics

30.05.2016 | Power and Electrical Engineering

Roadmap for better protection of Borneo’s cats and small carnivores

30.05.2016 | Ecology, The Environment and Conservation

Rosetta’s comet contains ingredients for life

30.05.2016 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>