Featured Research

from universities, journals, and other organizations

Rescuing Brain Cells In Stroke Patients From The Brink Of Suicide

Date:
August 24, 1999
Source:
University Of Rochester
Summary:
In a bid to persuade fickle brain cells to live, University of Rochester scientists have enlisted an unlikely ally: the herpes virus.

For several days after a patient suffers a stroke, brain cells are bombarded with molecular "pro-death" signals carrying such bad news about the brain environment that the cells are tempted, even urged by other molecules, to commit suicide. Many do. It's the main reason why most strokes aren't limited to a tiny area of the brain but damage a larger region as well.

In a bid to persuade fickle brain cells to live, University of Rochester scientists have enlisted an unlikely ally: the herpes virus. In an article published August 15 in the Journal of Neuroscience, the team announces a series of experiments where it used the virus to modify brain cells from mice, making the cells more resistant to death after a stroke. Like psychologists talking a despondent man down from the ledge, scientists kept cells from preventing suicide by thwarting the molecular machinery normally involved in persuading cells to self-destruct in a process known as apoptosis.

Once the brain has been traumatized by the low oxygen levels, or hypoxia, that stroke causes by choking off the blood supply, it unleashes a flurry of molecular signals encouraging still-healthy cells to kill themselves, magnifying the effects of the initial attack. The widespread self-destruction takes places for days or even a week after the initial stroke. It's a big reason why strokes are the leading cause of long-term disability in the United States, where there are about 4 million stroke survivors, roughly the same number of people as have Alzheimer's disease.

"Stroke is all about how cells deal with hypoxia," says neuroscientist Howard Federoff, M.D. Ph.D., who did the study with graduate student Marc Halterman and dermatologist Craig Miller, M.D. Ph.D. "Do they adapt and survive, or do they withdraw and commit suicide?" asks Federoff, who has developed a highly advanced system for using the herpes virus -- long the bane of cold sore sufferers everywhere -- to manipulate genes in the nervous system.

Today, the only real treatment for stroke is a set of drugs that break up the blood clots that cause most strokes. Such drugs are only useful if patients get to the hospital within a few hours of a "brain attack," and just a tiny percentage of patients ultimately receives them. There are no drugs approved for use in humans to help save the cells in the siege that follows in a broad area known as the penumbra, the area surrounding the initial site of stroke.

"Patients who arrive at the hospital too late to be candidates for clot-busters might be candidates for a drug useful during this window of opportunity, to protect cells that will go on to die if you don't intervene," says Halterman, who is earning both his M.D. and his Ph.D. at the University of Rochester School of Medicine and Dentistry.

While dozens of compounds are being studied to help protect brain cells after a stroke, they are not used clinically because none has been shown to be both safe and effective in humans, says Curtis Benesch, M.D., director of the Stroke Program at the University's Strong Memorial Hospital. "Right now treatment for acute stroke consists of two things: restoring blood flow, and 'housekeeping' details, like making sure glucose and blood pressure are at optimum levels," says Benesch. "A compound to help nearby cells cope with the shock of low oxygen would give doctors a new way to try to save patients from the years of disability that a stroke often causes."

As one step toward such a drug, Federoff's team asked the question: What brings a brain cell to suicide? Through a series of painstaking experiments funded by the National Institutes of Health, Halterman showed that two genes that help make cancerous tumor cells tough to kill are also involved in causing brain damage after a stroke.

The genes, HIF1a and p53, play a vital role in our everyday lives. The normal version of P53 helps our bodies suppress cancer, and HIF1a helps us cope with low-oxygen conditions, spurring the bone marrow to produce more oxygen-carrying red blood cells. Each also plays an important role in tumor cells, where HIF1a and a mutated copy of p53 help cancer cells survive in places in the body where oxygen is in short supply, like the inside of large tumors.

In the brain, the Rochester team found that both HIF1a and p53 play a role in convincing stressed cells to commit suicide. When the team used the herpes virus to shuttle into brain cells from mice a modified, defective version of the normal HIF1a gene, most of the cells opted not to commit apoptosis when stressed by low oxygen levels. Fewer of the neurons in a cell culture model of stroke died -- about half the neurons that normally would have died survived -- when HIF1a`s activity was taken out of the picture.

The scientists suspect that a cell's decision to commit suicide or not involves signals sent by HIF1a and p53 from the mitochondria, the cellular energy source that needs oxygen to keep the cell alive. HIF1a acts as an oxygen sensor that helps the cell decide whether to adapt to hypoxia, or instead activate p53 as part of a built-in suicide program to kill itself in a violent burst.

"If we can understand how that precise switch is regulated, it would open the door to some very interesting neuroprotective compounds to treat stroke," says Federoff, who is also director of the Medical Center's Center on Aging and Developmental Biology and chief of the Division of Molecular Medicine and Gene Therapy.


Story Source:

The above story is based on materials provided by University Of Rochester. Note: Materials may be edited for content and length.


Cite This Page:

University Of Rochester. "Rescuing Brain Cells In Stroke Patients From The Brink Of Suicide." ScienceDaily. ScienceDaily, 24 August 1999. <www.sciencedaily.com/releases/1999/08/990824074159.htm>.
University Of Rochester. (1999, August 24). Rescuing Brain Cells In Stroke Patients From The Brink Of Suicide. ScienceDaily. Retrieved September 16, 2014 from www.sciencedaily.com/releases/1999/08/990824074159.htm
University Of Rochester. "Rescuing Brain Cells In Stroke Patients From The Brink Of Suicide." ScienceDaily. www.sciencedaily.com/releases/1999/08/990824074159.htm (accessed September 16, 2014).

Share This



More Health & Medicine News

Tuesday, September 16, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

EU Ministers and Experts Meet to Discuss Ebola Reponse

EU Ministers and Experts Meet to Discuss Ebola Reponse

AFP (Sep. 15, 2014) The European Commission met on Monday to coordinate aid that the EU can offer to African countries affected by the Ebola outbreak. Duration: 00:58 Video provided by AFP
Powered by NewsLook.com
Despite The Risks, Antibiotics Still Overprescribed For Kids

Despite The Risks, Antibiotics Still Overprescribed For Kids

Newsy (Sep. 15, 2014) A new study finds children are prescribed antibiotics twice as often as is necessary. Video provided by Newsy
Powered by NewsLook.com
FDA Eyes Skin Shocks Used at Mass. School

FDA Eyes Skin Shocks Used at Mass. School

AP (Sep. 15, 2014) The FDA is considering whether to ban devices used by the Judge Rotenberg Educational Center in Canton, Massachusetts, the only place in the country known to use electrical skin shocks as aversive conditioning for aggressive patients. (Sept. 15) Video provided by AP
Powered by NewsLook.com
Respiratory Virus Spreads To Northeast, Now In 21 States

Respiratory Virus Spreads To Northeast, Now In 21 States

Newsy (Sep. 14, 2014) The respiratory virus Enterovirus D68, which targets children, has spread from the Midwest to 21 states. 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