Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Discovery changes ideas about damage from strokes

13.01.2004


In experiments in the laboratory and with mice, the Johns Hopkins researchers found that the chemical prostaglandin-E2 protects brain cells from damage. The finding was completely unexpected, the researchers say, because prostaglandin-E2 causes damage in other tissues and is made by an enzyme, COX-2, known to wreak havoc in the brain after injury. The findings appear in the Jan. 7 issue of the Journal of Neuroscience.



"It’s kind of paradoxical, that the product of an enzyme that causes damage is itself beneficial," says Katrin Andreasson, M.D., an assistant professor of neurology and of neuroscience. "It’s possible that future treatments for stroke might use drugs to block COX-2 and enhance the effects of prostaglandin-E2, providing sort of a double whammy of protection.

"Prostaglandins have not previously been implicated in reducing damage from stroke, so our finding provides a completely new strategy for tackling and understanding the condition," she adds.


In experiments with individual brain cells and with brain slices from mice, the researchers discovered that prostaglandin-E2 (PGE2), one of many related molecules created by COX-2, protects brain cells traumatized by over-stimulation or by insufficient oxygen. Furthermore, in genetically engineered mice lacking one of the receptors, or docking points, for this prostaglandin, stroke damage was much greater than in normal mice, the researchers report.

"Together, these results provide very strong evidence that PGE-2 is indeed protective in the brain even though it may not be elsewhere in the body," says Andreasson, who obtained the genetically engineered mice from Richard Breyer at Vanderbilt University School of Medicine.

After their surprising discovery, the research team searched for why PGE2 is a "good guy" in the brain. Their experiments showed that stimulation of PGE2’s receptor increases production of a molecule called cyclic-AMP, which is known to help the brain. Other effects of PGE2, such as anti-inflammatory effects, may also contribute to its protective abilities in the brain, says Andreasson.

"We think that COX-2 products that increase cyclic-AMP may prove to be protective, like PGE2, while those that lower cyclic-AMP may contribute to COX-2’s known negative effects on brain damage from stroke," she says. "We’re still working on it."

About 4 million Americans are currently living with the effects of stroke, in which blood flow and oxygen delivery to the brain are interrupted by blockage or breakage of a blood vessel. At first, brain cells are shocked, not killed, but their chances of recovery decrease rapidly as time passes.

If given within an hour of the stroke, a drug called t-PA can prevent extensive damage by dissolving the blood clot that caused the stroke. However, finding a way to intervene later on -- for patients whose symptoms aren’t immediately recognized or who are more than an hour from a hospital -- could dramatically improve recovery and reduce the financial burden of strokes, which the National Stroke Association estimates is roughly $43 billion per year in the United States.

"We still need to determine whether stimulating the PGE2 receptor hours after a stroke can protect mice from damage," says Andreasson, who is conducting some of those studies now. "If so, pursuing this prostaglandin as a potential clinical target will be of great importance."

COX-2 has a significant role in brain damage after stroke in mice, and Andreasson has been searching for how exactly COX-2 causes damage. Scientists know that COX-2 is involved in creating inflammation, or swelling (drugs like Celebrex and Vioxx inhibit COX-2 and are widely prescribed for arthritis and other inflammatory conditions), but its activity leads to the production of a number of different molecules which could be more directly responsible for its effects. Andreasson and her colleagues are continuing to evaluate the effects of other products of COX-2.


The studies were funded by the American Federation for Aging Research, the American Heart Association, and the National Institute on Neurological Diseases and Stroke. Authors on the report are Andreasson, Louise McCullough, Liejun Wu, Norman Haughey, Xibin Liang, Tracey Hand and Qian Wang of The Johns Hopkins University School of Medicine; and Breyer of Vanderbilt.

Joanna Downer | EurekAlert!
Further information:
http://www.jneurosci.org/
http://www.hopkinsmedicine.org/

More articles from Health and Medicine:

nachricht 'Living bandages': NUST MISIS scientists develop biocompatible anti-burn nanofibers
16.02.2018 | National University of Science and Technology MISIS

nachricht New process allows tailor-made malaria research
16.02.2018 | Eberhard Karls Universität Tübingen

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: In best circles: First integrated circuit from self-assembled polymer

For the first time, a team of researchers at the Max-Planck Institute (MPI) for Polymer Research in Mainz, Germany, has succeeded in making an integrated circuit (IC) from just a monolayer of a semiconducting polymer via a bottom-up, self-assembly approach.

In the self-assembly process, the semiconducting polymer arranges itself into an ordered monolayer in a transistor. The transistors are binary switches used...

Im Focus: Demonstration of a single molecule piezoelectric effect

Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale

Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...

Im Focus: Hybrid optics bring color imaging using ultrathin metalenses into focus

For photographers and scientists, lenses are lifesavers. They reflect and refract light, making possible the imaging systems that drive discovery through the microscope and preserve history through cameras.

But today's glass-based lenses are bulky and resist miniaturization. Next-generation technologies, such as ultrathin cameras or tiny microscopes, require...

Im Focus: Stem cell divisions in the adult brain seen for the first time

Scientists from the University of Zurich have succeeded for the first time in tracking individual stem cells and their neuronal progeny over months within the intact adult brain. This study sheds light on how new neurons are produced throughout life.

The generation of new nerve cells was once thought to taper off at the end of embryonic development. However, recent research has shown that the adult brain...

Im Focus: Interference as a new method for cooling quantum devices

Theoretical physicists propose to use negative interference to control heat flow in quantum devices. Study published in Physical Review Letters

Quantum computer parts are sensitive and need to be cooled to very low temperatures. Their tiny size makes them particularly susceptible to a temperature...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

2nd International Conference on High Temperature Shape Memory Alloys (HTSMAs)

15.02.2018 | Event News

Aachen DC Grid Summit 2018

13.02.2018 | Event News

How Global Climate Policy Can Learn from the Energy Transition

12.02.2018 | Event News

 
Latest News

Contacting the molecular world through graphene nanoribbons

19.02.2018 | Materials Sciences

When Proteins Shake Hands

19.02.2018 | Materials Sciences

Cells communicate in a dynamic code

19.02.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>