New class of potential drugs inhibits inflammation in brain

February 14, 2012 by Quinn Eastman

Scientists at Emory University School of Medicine have identified a new group of compounds that may protect brain cells from inflammation linked to seizures and neurodegenerative diseases.

The compounds block signals from EP2, one of the four receptors for , which is a hormone involved in processes such as fever, childbirth, digestion and . Chemicals that could selectively block EP2 were not previously available. In animals, the EP2 blockers could markedly reduce the injury to the brain induced after a prolonged seizure, the researchers showed.

The results were published online this week in the Early Edition.

"EP2 is involved in many disease processes where inflammation is showing up in the nervous system, such as epilepsy, stroke and ," says senior author Ray Dingledine, PhD, chairman of Emory's Department of Pharmacology. "Anywhere that inflammation is playing a role via EP2, this class of compounds could be useful. Outside the brain, EP2 blockers could find uses in other diseases with a prominent inflammatory component such as cancer and ."

Prostaglandins are the targets for non-steroid anti-inflammatory drugs (NSAIDs) such as aspirin and ibuprofen. NSAIDSs inhibit enzymes known as cyclooxygenases, the starting point for generating prostaglandins in the body. Previous research indicates that drugs that inhibit cyclooxygenases can have harmful side effects. For example, sustained use of aspirin can weaken the , coming from prostaglandins' role in the stomach. Even drugs designed to inhibit only cyclooxygenases involved in pain and inflammation, such as Vioxx, have displayed cardiovascular side effects.

Dingledine's team's strategy was to bypass cyclooxygenase enzymes and go downstream, focusing on one set of molecules that relay signals from prostaglandins. Working with Yuhong Du in the Emory Discovery Center, postdoctoral fellows Jianxiong Jiang, Thota Ganesh and colleagues sorted through a library of 262,000 compounds to find those that could block signals from the EP2 prostaglandin receptor but not related receptors. One of the compounds could prevent damage to neurons in mice after "status epilepticus," a prolonged drug-induced seizure used to model the neurodegeneration linked to epilepsy.

The team found that a family of related compounds had similar protective effects.

Dingledine says that the compounds could become valuable tools for exploring new ways to treat neurological diseases. However, given the many physiological processes prostaglandins regulate, more tests are needed, he says. Prostaglandin E2 is itself a drug used to induce labor in pregnant women, and female mice engineered to lack the EP2 receptor are infertile, so the compounds would need to be tested for effects on reproductive organs, for example.

Explore further: Sex hormone precursor inhibits brain inflammation

More information: J. Jiang et al. Small molecule antagonist reveals seizure-induced mediation of neuronal injury by prostaglandin E2 receptor subtype EP2. PNAS 2012, doi:10.1073/pnas.1120195109

Related Stories

Sex hormone precursor inhibits brain inflammation

May 12, 2011

Researchers at the University of California, San Diego School of Medicine have discovered a steroid hormone that inhibits inflammation in the brain. The findings, to be published in the May 13 issue of the journal Cell, have ...

Recommended for you

Umbilical cells help eye's neurons connect

November 24, 2015

Cells isolated from human umbilical cord tissue have been shown to produce molecules that help retinal neurons from the eyes of rats grow, connect and survive, according to Duke University researchers working with Janssen ...

Brain connections predict how well you can pay attention

November 24, 2015

During a 1959 television appearance, Jack Kerouac was asked how long it took him to write his novel On The Road. His response – three weeks – amazed the interviewer and ignited an enduring myth that the book was composed ...

No cable spaghetti in the brain

November 24, 2015

Our brain is a mysterious machine. Billions of nerve cells are connected such that they store information as efficiently as books are stored in a well-organized library. To this date, many details remain unclear, for instance ...

Neurons encoding hand shapes identified in human brain

November 23, 2015

Neural prosthetic devices, which include small electrode arrays implanted in the brain, can allow paralyzed patients to control the movement of a robotic limb, whether that limb is attached to the individual or not. In May ...

Wireless sensor enables study of traumatic brain injury

November 23, 2015

A new system that uses a wireless implant has been shown to record for the first time how brain tissue deforms when subjected to the kind of shock that causes blast-induced trauma commonly seen in combat veterans.

Neuroscientists reveal how the brain can enhance connections

November 18, 2015

When the brain forms memories or learns a new task, it encodes the new information by tuning connections between neurons. MIT neuroscientists have discovered a novel mechanism that contributes to the strengthening of these ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.