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New understanding of why brain cells die after stroke will lead to development of new treatments
TORONTO, Dec. 24 /CNW/ - Scientists at Toronto Western Hospital and the
University of Toronto have found a major mechanism that causes brain cells to
die from stroke. They discovered that when brain cells are deprived of oxygen
and vital nutrients, as happens to parts of the brain affected by a stroke, a
special channel on the surface of those brain cells is activated, triggering a
lethal chain reaction. The channel, called TRPM7, when activated causes brain
cells to produce large quantities of free radicals - toxic molecules that
break down the cell's DNA, proteins, and other components. Free radicals also
cause TRPM7 to become even more active, causing massive overproduction of free
radicals, resulting in death of the brain cell.
In a study published in the December 26 issue of Cell, an international
science journal, the scientists also report that they have found a way to
interfere with this lethal chain reaction. While brain cells can only survive
for a few minutes without oxygen, interfering with the activity of TRPM7
allows brain cells to survive for more than three hours without oxygen and
vital nutrients.
With this new understanding, there is now an opportunity to develop new
medications that prevent activation of the TRPM7 channel. It will take
approximately three years to develop a medication.
"This is a quantum leap forward in understanding how stroke causes brain
damage," says Dr. Michael Tymianski, neurosurgeon at the Krembil Neuroscience
Centre at Toronto Western Hospital and associate professor of surgery and
physiology at the University of Toronto. "Now we can see the bigger picture of
why brain cells die from stroke."
"This project is a primary example of how basic and clinical scientists
can come together as an effective research team to tackle the major health
problem of stroke," says Dr. John MacDonald, chair of the department of
physiology, Faculty of Medicine at the University of Toronto. "We are also
very excited to explore the many potential functions of TRPM7 channels in the
brain."
Until now, scientists thought they understood why brain cells die when
deprived of oxygen and essential nutrients. Past research suggested that the
major culprit was glutamate, an amino acid normally used by brain cells to
communicate by carrying signals from one brain cell to the next. Dying brain
cells release glutamate, which attaches to a special channel called the NMDA
receptor located on the surface of the neighbouring brain cells. This causes
the NMDA channel to open and allows an influx of calcium ions into the brain
cell. For years, it was thought that this sequence of events caused brain
cells to die from stroke.
For this reason, many experimental medications for treating strokes were
aimed at blocking the effects of glutamate on NMDA receptors. Although it
worked in the lab, the medications failed to reduce brain damage in humans.
Despite three decades of research that pointed to glutamate as the culprit in
cell death, the failure of these medications remained a mystery. To solve this
mystery, Drs. Tymianski and MacDonald went back to the drawing board and
discovered that glutamate was only one part of the reason why brain cells die
from stroke.
"We have significant experience in translating such basic discoveries
into drugs that might help patients," says Dr. Tymianski. "With this new
knowledge, we will now focus on developing medications that we can inject into
stroke patients up to several hours after a stroke. These medications will
prevent the consequences of activating TRPM7, extend the life of brain cells
after a stroke, and help improve the outcome of patients suffering from a
stroke."
As the fourth most common cause of death in Canada, and the second
leading cause of death in the world, stroke kills about 16,000 Canadians every
year. Stroke is a major cause of disability, as people who survive strokes
suffer irreparable damage to their brain cells. These effects can include
partial paralysis, problems with thinking, problems with language, and
difficulty with movement. Approximately 300,000 Canadians live with the
effects of stroke. The warning signs of a stroke include sudden weakness,
trouble speaking, vision problems, headache, and dizziness.
This research was funded by grants from the Canadian Institutes of Health
Research, the Ontario Heart and Stroke Foundation, and the National Institutes
of Health of the United States of America.
Toronto Western Hospital has been serving the health care needs of its
culturally diverse community for more than 100 years. Today, the hospital
provides highly specialized tertiary care to people from surrounding areas and
across Canada. Home to the Krembil Neuroscience Centre, one of the largest
combined clinical and research neurological facilities in North America, the
hospital also offers a community and population health program and expertise
in musculoskeletal health and arthritis. Toronto Western Hospital is one of
three hospitals - including Toronto General Hospital and Princess Margaret
Hospital - that make up University Health Network, a teaching hospital of the
University of Toronto.
The University of Toronto (U of T), Canada's leading research university
with over 60,000 students, was founded in 1872 by British royal charter. For
the tenth consecutive year, U of T has taken the top spot among
medical/doctoral universities in the annual Maclean's magazine university
ranking. The university now comprises 31 divisions, colleges and faculties on
three campuses, including 14 professional faculties, numerous research centres
and Canada's largest library system - one of the top research libraries in
North America. U of T's Department of Physiology is the largest and most
research-intensive university physiology departments in Canada and has
research and training partnerships with numerous hospital-based research
institutes.
Images, diagram, and flow chart are available.
For further information: Jennifer Kohm, Communications Specialist,
Toronto Western Hospital, telephone: (416) 603-5323, pager: (416) 867-0770,
jennifer.kohm@uhn.on.ca |
