Copyright 2004 Scripps Howard, Inc.  
Scripps Howard News Service
July 7, 2004, Wednesday 12:40 PM Eastern Time
SECTION: DOMESTIC NEWS
LENGTH: 470 words
SOURCE: Scripps Howard News Service
BYLINE: LEE BOWMAN

Researchers have found out why some brain cells are vulnerable to damage from oxygen starvation following stroke and explained why experimental drugs that attempt to thwart death of the cells haven't worked.

A team led by YouMing Lu of the University of Calgary focused on neurons in the hippocampus, a region of the brain central to the formation of memories.

The findings could also lead to drugs that protect vulnerable brain cells in people suffering from amyotrophic lateral sclerosis, or Lou Gerhig's disease, since that damage also results from the same sort of defect, Lu noted.

The culprit is a particular type of pathway through the membranes of brain cells that controls the flow of calcium to their interior. This channel, or receptor, is known to be involved in causing neurons to die when denied oxygen during a stroke.

Yet clinical trials of drugs designed to block those receptors have failed, because the drugs also block the channels in brain cells that aren't vulnerable to death from stroke.

Clots and other blockages in the arteries of the brain cause 80 percent of all strokes (the rest are the result of burst arteries). Strokes are the third-leading cause of death and disability in the United States, striking more than 600,000 victims each year.

Currently, the main treatment for stroke victims is a class of drugs that works quickly to break up the clot and restore blood flow to the oxygen-starved region of the brain. But these drugs can have dangerous side effects, including uncontrolled bleeding. No treatments to protect the brain cells in the isolated area have yet been proven to work.

The Canadian researchers report Thursday in the journal Neuron that they found vulnerable brain cells have channels that allow an unusual cascade of calcium and zinc inside them, activating machinery that causes the cells to die.

Lu's team further isolated this problem to a specific protein that dictates how permeable the cell's channels are to calcium. In rat experiments, they found they could prevent injury to the vulnerable cells by introducing a different form of the protein, allowing cells to keep calcium out.

Lu said that since the modified protein doesn't disrupt other cells, it is "a promising therapeutic target for stroke."

The researchers also discovered a second possible avenue to solve the problem. Other researchers had discovered that artery-blocking strokes reduced the activity of a gene that controls production of the calcium channel protein.

When Lu and his colleagues inserted a version of the gene that is always activated, it protected the vulnerable neurons in rat brains from the effects of an artificially induced stroke.

On the Net: www.neuron.org