Currents


Herpes virus may help stroke patients

F or 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, Medical Center scientists have enlisted an unlikely ally: the herpes virus. In an article published August 15 in the Journal of Neuroscience, the team announced 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. Scientists kept cells from committing 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 place 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 who have Alzheimer's disease.

"Stroke is all about how cells deal with hypoxia," said neuroscientist Howard Federoff, director of URMC's Center on Aging and Developmental Biology and chief of the Division of Molecular Medicine and Gene Therapy. He conducted the study with graduate student Marc Halterman and dermatologist Craig Miller. "Do they adapt and survive, or do they withdraw and commit suicide?" asked Federoff, who has developed a highly advanced system for using the herpes virus 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 receive 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," said Halterman, who is earning both his M.D. and Ph.D. at the School of Medicine and Dentistry.

While dozens of compounds are being studied to help protect brain cells after a stroke, they're not used clinically because none has been shown to be both safe and effective in humans, said Curtis Benesch, director of the Stroke Program at 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," he said. "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."

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