Featured Research

from universities, journals, and other organizations

Possible trigger for multiple sclerosis nerve damage

Date:
November 27, 2012
Source:
NIH/National Institute of Neurological Disorders and Stroke
Summary:
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.

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.

"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.


Story Source:

The above story is based on materials provided by NIH/National Institute of Neurological Disorders and Stroke. Note: Materials may be edited for content and length.


Journal Reference:

  1. Dimitrios Davalos, Jae Kyu Ryu, Mario Merlini, Kim M. Baeten, Natacha Le Moan, Mark A. Petersen, Thomas J. Deerinck, Dimitri S. Smirnoff, Catherine Bedard, Hiroyuki Hakozaki, Sara Gonias Murray, Jennie B. Ling, Hans Lassmann, Jay L. Degen, Mark H. Ellisman, Katerina Akassoglou. Fibrinogen-induced perivascular microglial clustering is required for the development of axonal damage in neuroinflammation. Nature Communications, 2012; 3: 1227 DOI: 10.1038/ncomms2230

Cite This Page:

NIH/National Institute of Neurological Disorders and Stroke. "Possible trigger for multiple sclerosis nerve damage." ScienceDaily. ScienceDaily, 27 November 2012. <www.sciencedaily.com/releases/2012/11/121127154215.htm>.
NIH/National Institute of Neurological Disorders and Stroke. (2012, November 27). Possible trigger for multiple sclerosis nerve damage. ScienceDaily. Retrieved July 23, 2014 from www.sciencedaily.com/releases/2012/11/121127154215.htm
NIH/National Institute of Neurological Disorders and Stroke. "Possible trigger for multiple sclerosis nerve damage." ScienceDaily. www.sciencedaily.com/releases/2012/11/121127154215.htm (accessed July 23, 2014).

Share This




More Health & Medicine News

Wednesday, July 23, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Courts Conflicted Over Healthcare Law

Courts Conflicted Over Healthcare Law

AP (July 22, 2014) Two federal appeals courts issued conflicting rulings Tuesday on the legality of the federally-run healthcare exchange that operates in 36 states. (July 22) Video provided by AP
Powered by NewsLook.com
Why Do People Believe We Only Use 10 Percent Of Our Brains?

Why Do People Believe We Only Use 10 Percent Of Our Brains?

Newsy (July 22, 2014) The new sci-fi thriller "Lucy" is making people question whether we really use all our brainpower. But, as scientists have insisted for years, we do. Video provided by Newsy
Powered by NewsLook.com
Scientists Find New Way To Make Human Platelets

Scientists Find New Way To Make Human Platelets

Newsy (July 22, 2014) Boston scientists have discovered a new way to create fully functioning human platelets using a bioreactor and human stem cells. Video provided by Newsy
Powered by NewsLook.com
Gilead's $1000-a-Pill Drug Could Cure Hep C in HIV-Positive People

Gilead's $1000-a-Pill Drug Could Cure Hep C in HIV-Positive People

TheStreet (July 21, 2014) New research shows Gilead Science's drug Sovaldi helps in curing hepatitis C in those who suffer from HIV. In a medical study, the combination of Gilead's Hep C drug with anti-viral drug Ribavirin cured 76% of HIV-positive patients suffering from the most common hepatitis C strain. Hepatitis C and related complications have been a top cause of death in HIV-positive patients. Typical medication used to treat the disease, including interferon proteins, tended to react badly with HIV drugs. However, Sovaldi's %1,000-a-pill price tag could limit the number of patients able to access the treatment. TheStreet's Keris Lahiff reports from New York. Video provided by TheStreet
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins