thestar.com
Dec. 26, 2003. 08:02 AM
Research finds key to stroke damage
Toronto team spots missing link
Cell life extended up to three hours
KAREN PALMER
PUBLIC HEALTH REPORTER
Toronto researchers have discovered the key to keeping brain cells alive much longer during a stroke, opening the door for new treatments that would make the brain resistant to a stroke's debilitating effects.
Five years of study at Toronto Western hospital and the University of Toronto determined that an ion channel on the surface of brain cells is switched on when the cells are deprived of oxygen and vital nutrients, as happens during a stroke.
That channel then funnels a flood of toxins into the cells, killing them, and leading to the kind of brain damage that can leave stroke sufferers paralyzed.
Blocking the channel, known as TRPM7, extends the time doctors have to treat the brain's impasse and save brain tissue.
"Normally (cells) die if they're exposed to a few minutes of oxygen and glucose deprivation. By blocking these few pathways, we were able to make tissues survive in the absence of oxygen and glucose for over three hours," said Dr. Michael Tymianski, a neurosurgeon at Toronto Western hospital, who made the discovery along with John MacDonald, a professor of physiology at the University of Toronto.
The finding, published today in the journal Cell, provides the missing link in cell research to a way to keep brain tissue alive.
"What we've missed in the past — the big gap in our knowledge — was the knowledge about this ion channel," Tymianski said.
"It can make a huge difference in the health care of society," he said, noting that stroke is the leading cause of adult disability in Canada and the fourth-leading cause of death.
"Clot-busting medications are the only treatment we have, but only 2 per cent (of stroke patients) make it to hospital in time for clot-busting drugs to be given," he said.
What happens in the brain when it's deprived of oxygen has befuddled scientists for years.
The after-effects, including paralysis, memory loss and slurred speech, are all too evident. Depending on how much tissue was damaged, the severity of a stroke can range from nearly nothing to lethal.
Almost 30 years ago, researchers decided brain cell death during a stroke was caused by neurons releasing too much glutamate, which in turn made cells susceptible to too much calcium and other free radical ions.
But treatments based on that theory couldn't stop brain cells from dying. "When clinical trials for stroke drugs began to fail one after another, we decided to go back to the drawing board to try to figure out why, whether there's been something we missed," Tymianski said.
They began replicating the early experiments and treating cells with drugs that worked in lab experience, but not in practice. They found cells that survived for a short time still died, despite the treatment, and decided there must be something more going on inside the cell.
Using grants from the Canadian Institute for Health Research, the Heart & Stroke Foundation and even the U.S. National Institutes for Health, Tymianski, MacDonald and their research team returned to basic biological techniques to build a molecular profile of the channel, without knowing they were describing an ion channel.
It wasn't until they came across a 2001 article about cloned ion channels in the journal Nature that they knew what they were dealing with.
"Clinicians never quite understood why previous treatments didn't work, despite excellent research showing we were on the right track," he said. "At this point, having added this major piece to the puzzle, I think it will get us back on track."
Tymianski figures it'll take scientists a mere three years to turn this discovery into a drug, one that ideally could be administered by paramedics as they rush stroke patients to hospital.
The discovery could also lead to treatments for all kinds of disorders where lack of blood flow is the root of the problem, including mini-strokes, brain trauma, glaucoma, heart disease and blood pressure problems. |
