Researchers identify novel mechanism to reduce nervous system inflammation

Sep 24, 2008

Researchers at Georgetown University Medical Center have discovered a new way to limit inflammation caused by the activation of microglia - key immune cells in the brain. Although the role of such cells is to "clean up damage" after injury, they often worsen the damage by releasing toxic inflammatory factors.

In the October issue of the journal Glia, now published online, the scientists say that the type of chemical they used to deactivate these cells could possibly be developed as a drug to treat a variety of acute and chronic disorders marked by brain cell damage – including stroke, head and spinal cord injury, and possibly Alzheimer's disease and Parkinson's disease.

"Inflammation associated with the activation of microglial cells is an important factor that appears to contribute to tissue damage and disability in many of the important neurodegenerative disorders. By decreasing this inflammatory response, tissue loss after injury can be reduced. Thus, what we found in this study has important potential therapeutic implications for the treatment of a number of important neurological disorders," says the study's senior investigator, Alan I. Faden, M.D., a professor of neuroscience and director of the Laboratory for the Study of Central Nervous System Injury.

The research, led by investigator Kimberly Byrnes, Ph.D., an assistant professor in Faden's laboratory, centered on microglial cells, which react against pathogens that invade the brain, and also remove foreign material and damaged cells.

Byrnes describes microglial cells as just a little too good at their jobs. "They overdo it, perhaps because they don't have very good stop signals. They secrete a number of toxic chemicals designed to clear up infections and damaged tissue-- but in the process they can kill sensitive brain cells."

In this study, Byrnes, Faden and a team of four other researchers looked to see whether microglial cells express a certain receptor on their surface that Faden and his laboratory had previously found could be turned on in brain neurons to prevent cell death in response to injury. The receptor, the group I metabotropic glutamate receptor 5 (mGluR5), which also plays a critical role in modulating pain and addiction, was previously found in other types of brain cells.

The researchers found the receptor protein in microglia in cell culture. "That's a first," Byrnes says. They then showed that a selective activator of this receptor type, CHPG, could turn off microglial activity. This is the same chemical that Faden discovered could shut down certain kinds of suicide cell death (apoptosis) in neurons.

"We found that if we stimulate just this receptor, we can markedly reduce microglial release of key inflammatory factors and the ability of activated microglia to kill nerve cells," Byrnes says.

The receptor, therefore, appears to be a switch-off mechanism, a brake on the damaging effects of microglial activity. "This is possibly a way that the brain has designed to turn microglia off, but the problem is that these cells get many other signals that keep them turned on after injury."

Treating brain injury with a selective compound may be challenging, the researchers add. "Microglia also releases good chemicals, such as growth factors, to promote nerve cell regrowth and regeneration, so the trick will be to discretely use it after injury for a period of time."

But brain and spinal cord injury studies in animals, conducted after the present experiments were completed, have been very encouraging, Byrnes says. Those studies have not yet been published.

Source: Georgetown University

Explore further: Goat to be cloned to treat rare genetic disorder

add to favorites email to friend print save as pdf

Related Stories

'First aid' for brain cells comes from blood

Apr 16, 2009

In acute ischemic stroke, the blood supply to the brain is restricted. Initially, brain cells die from lack of oxygen. In addition, ischemia activates harmful inflammatory processes in the affected area of the brain. For ...

Recommended for you

Researchers transplant regenerated oesophagus

17 hours ago

Tissue engineering has been used to construct natural oesophagi, which in combination with bone marrow stem cells have been safely and effectively transplanted in rats. The study, published in Nature Communications, shows ...

User comments : 0

More news stories

Low Vitamin D may not be a culprit in menopause symptoms

A new study from the Women's Health Initiative (WHI) shows no significant connection between vitamin D levels and menopause symptoms. The study was published online today in Menopause, the journal of The North American Menopa ...

Tech giants look to skies to spread Internet

The shortest path to the Internet for some remote corners of the world may be through the skies. That is the message from US tech giants seeking to spread the online gospel to hard-to-reach regions.

Patent talk: Google sharpens contact lens vision

(Phys.org) —A report from Patent Bolt brings us one step closer to what Google may have in mind in developing smart contact lenses. According to the discussion Google is interested in the concept of contact ...

Wireless industry makes anti-theft commitment

A trade group for wireless providers said Tuesday that the biggest mobile device manufacturers and carriers will soon put anti-theft tools on the gadgets to try to deter rampant smartphone theft.