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 Study tracks inner workings of the brain with new biosensor
16.08.2018 | Rheinische Friedrich-Wilhelms-Universität Bonn

nachricht Foods of the future
15.08.2018 | Georg-August-Universität Göttingen

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: Color effects from transparent 3D-printed nanostructures

New design tool automatically creates nanostructure 3D-print templates for user-given colors
Scientists present work at prestigious SIGGRAPH conference

Most of the objects we see are colored by pigments, but using pigments has disadvantages: such colors can fade, industrial pigments are often toxic, and...

Im Focus: Unraveling the nature of 'whistlers' from space in the lab

A new study sheds light on how ultralow frequency radio waves and plasmas interact

Scientists at the University of California, Los Angeles present new research on a curious cosmic phenomenon known as "whistlers" -- very low frequency packets...

Im Focus: New interactive machine learning tool makes car designs more aerodynamic

Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.

When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...

Im Focus: Robots as 'pump attendants': TU Graz develops robot-controlled rapid charging system for e-vehicles

Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.

Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....

Im Focus: The “TRiC” to folding actin

Proteins must be folded correctly to fulfill their molecular functions in cells. Molecular assistants called chaperones help proteins exploit their inbuilt folding potential and reach the correct three-dimensional structure. Researchers at the Max Planck Institute of Biochemistry (MPIB) have demonstrated that actin, the most abundant protein in higher developed cells, does not have the inbuilt potential to fold and instead requires special assistance to fold into its active state. The chaperone TRiC uses a previously undescribed mechanism to perform actin folding. The study was recently published in the journal Cell.

Actin is the most abundant protein in highly developed cells and has diverse functions in processes like cell stabilization, cell division and muscle...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

LaserForum 2018 deals with 3D production of components

17.08.2018 | Event News

Within reach of the Universe

08.08.2018 | Event News

A journey through the history of microscopy – new exhibition opens at the MDC

27.07.2018 | Event News

 
Latest News

Smallest transistor worldwide switches current with a single atom in solid electrolyte

17.08.2018 | Physics and Astronomy

Robots as Tools and Partners in Rehabilitation

17.08.2018 | Information Technology

Climate Impact Research in Hannover: Small Plants against Large Waves

17.08.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>