Featured Research

from universities, journals, and other organizations

COX-2 Product Offers Good And Bad News In 'Test Tube' Strokes

Date:
February 20, 2005
Source:
Johns Hopkins Medical Institutions
Summary:
Laboratory studies at Johns Hopkins have revealed that certain products of the enzymes COX-1 and COX-2 can both protect and damage the brain. The findings, published in the February 2005 issue of the Journal of Neurochemistry, offer tantalizing clues to why drugs like Vioxx and Celebrex, which block COX-2, can ease arthritis but potentially harm the heart and brain.

Laboratory studies at Johns Hopkins have revealed that certain products of the enzymes COX-1 and COX-2 can both protect and damage the brain. The findings, published in the February 2005 issue of the Journal of Neurochemistry, offer tantalizing clues to why drugs like Vioxx and Celebrex, which block COX-2, can ease arthritis but potentially harm the heart and brain.

Katrin Andreasson, M.D., an assistant professor in the neurology and neuroscience departments at Hopkins, and lead author of the study, explains that the recent discoveries of cardiovascular complications with long-term use of some COX-2 inhibitors are thought to be due to blocking effects of "good" prostaglandins, which are the downstream products of COX activity, potentially leading to heart attacks and strokes. "Defining which prostaglandin pathways are good and which promote disease would help to design more specific therapeutics," she says.

In their latest laboratory studies, the Hopkins scientists discovered that the prostaglandin PGD2 has a protective or harmful effect in the brain depending on where it docks on a brain cell's surface. After brain cells experience the laboratory equivalent of a stroke, PDG2 can protect them from being killed if it binds to one docking point, or receptor, on the cells' surface, but causes them to die in greater numbers if it binds to a second receptor instead, the researchers report. Prostaglandins are involved in a wide variety of bodily activities including relaxation and contraction of muscles and blood vessels, control of blood pressure and inflammation.

"PGD2 is the most-produced prostaglandin in the brain," says Andreasson. "It trumps all of the rest. So we theorized that high levels are protective. But it was a surprise that it was so effective at protecting neurons."

Because the Hopkins team found that PGD2's positive effects generally outweigh its negative ones, the group speculates that PGD2 may provide a potential target for medicines to combat conditions involving brain damage, including stroke, Parkinson's disease and Alzheimer's disease.

In these neurologic diseases, nerve cell death is thought to be carried out in part by a huge release of glutamate, an important signaling molecule in the brain. In their experiments with brain cells and brain tissue from rats, the Hopkins researchers used glutamate to simulate the aftereffects of a stroke. After strokes and other injuries to the brain, levels of glutamate rise, triggering a number of chemical reactions, including an increase in COX-2 production and prostaglandin production. Increased COX-2 activity then leads to further neuron death.

The new findings come in the wake of two previous studies Andreasson has worked on, each finding unexpected protective roles for another prostaglandin produced by COX-2. In one, a different prostaglandin (PGE2) prevented brain cells from dying after a stroke. In the other, mice lacking a docking point for the PGE2 experienced strokes far more severe than normal animals.

Andreasson is now trying to determine if these prostaglandins have a similar protective effect in mouse models of Lou Gehrig's disease, in which excessive glutamate is believed to damage neurons, and will begin work to see if the beneficial side of PGD2 activity can outweigh its toxic activity.

###

The Hopkins studies were funded by the National Institute of Neurological Disorders and Stroke (NINDS) and the American Federation for Aging Research. Other authors of the study were Xibin Liang, Liejun Wu and Tracey Hand, all from the Johns Hopkins School of Medicine.


Story Source:

The above story is based on materials provided by Johns Hopkins Medical Institutions. Note: Materials may be edited for content and length.


Cite This Page:

Johns Hopkins Medical Institutions. "COX-2 Product Offers Good And Bad News In 'Test Tube' Strokes." ScienceDaily. ScienceDaily, 20 February 2005. <www.sciencedaily.com/releases/2005/02/050217224933.htm>.
Johns Hopkins Medical Institutions. (2005, February 20). COX-2 Product Offers Good And Bad News In 'Test Tube' Strokes. ScienceDaily. Retrieved April 25, 2014 from www.sciencedaily.com/releases/2005/02/050217224933.htm
Johns Hopkins Medical Institutions. "COX-2 Product Offers Good And Bad News In 'Test Tube' Strokes." ScienceDaily. www.sciencedaily.com/releases/2005/02/050217224933.htm (accessed April 25, 2014).

Share This



More Mind & Brain News

Friday, April 25, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Could Marijuana Use Lead To Serious Heart Problems?

Could Marijuana Use Lead To Serious Heart Problems?

Newsy (Apr. 24, 2014) A new study says marijuana use could lead to serious heart-related complications. Video provided by Newsy
Powered by NewsLook.com
Study Says Most Crime Not Linked To Mental Illness

Study Says Most Crime Not Linked To Mental Illness

Newsy (Apr. 22, 2014) A new study finds most crimes committed by people with mental illness are not caused by symptoms of their illness or disorder. Video provided by Newsy
Powered by NewsLook.com
How Smaller Plates And Cutlery Could Make You Feel Fuller

How Smaller Plates And Cutlery Could Make You Feel Fuller

Newsy (Apr. 22, 2014) NBC's "Today" conducted an experiment to see if changing the size of plates and utensils affects the amount individuals eat. Video provided by Newsy
Powered by NewsLook.com
Do We Get Nicer With Age?

Do We Get Nicer With Age?

Newsy (Apr. 22, 2014) A recent report claims personality can change over time as we age, and usually that means becoming nicer and more emotionally stable. Video provided by Newsy
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