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Public Release: 24-Mar-2005
Journal of Cerebral Blood Flow and Metabolism
Researchers discover molecule that causes secondary stroke
Scientists at the University of Cincinnati (UC) College of Medicine have
discovered the cause of a deadly type of secondary stroke known as
cerebral vasospasm. A constriction of the blood vessels in the brain,
cerebral vasospasm usually occurs three to 10 days following a massive
brain bleed known as hemorrhagic stroke. Sixty percent of patients who
survive the initial stroke develop vasospasm, and 40 percent of them die
from it.
National Institutes of Health, The Neuroscience Institute
Contact: Sheryl Hilton
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513-558-4553
University of Cincinnati
Public release date: 24-Mar-2005
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Contact: Sheryl Hilton
[log in to unmask]
513-558-4553
University of Cincinnati
Researchers discover molecule that causes secondary stroke
CINCINNATI--Scientists at the University of Cincinnati (UC) College of
Medicine have discovered the cause of a deadly type of secondary stroke
known as cerebral vasospasm.
A constriction of the blood vessels in the brain, cerebral vasospasm
usually occurs three to 10 days following a massive brain bleed known as
hemorrhagic stroke. Sixty percent of patients who survive the initial
stroke develop vasospasm, and 40 percent of them die from it.
Vasospasm, says neurology department researcher Joseph Clark, PhD,
results from a buildup of toxins caused by bleeding from the initial
stroke. "Normally the cerebral spinal fluid that envelopes the brain
carries off wastes and exchanges them for nutrients at what's called the
blood-brain barrier," Dr. Clark says. "After a hemorrhagic stroke,
however, toxins given off by the brain bleed contribute to the
development of specific molecules that later causes the constricting
vasospasm." A research team led by Dr. Clark has now identified the
molecules that trigger vasospasm, a breakthrough, he says, that "raises
hopes of developing not only new ways to treat the condition, but also a
diagnostic test to determine which hemorrhagic stroke survivors are at
greater risk."
Several spinal fluid components were suspected of causing the vasospasm,
Dr. Clark explains. They included hemoglobin, bilirubin and peroxidized
lipids, and a group of bilirubin oxidation products that the researchers
called BOXes.
Building on Dr. Clark's earlier studies in rats, the team measured each
of the suspect agents in 12 hemorrhagic stroke patients. Within 10 days,
four of the group suffered a secondary cerebral vasospasm. The same
patients were also found to have elevated levels of bilirubin and
significantly higher levels of BOXes.
One of the 12 who had elevated bilirubin, but hardly any BOXes, did not
experience a secondary stroke.
When bilirubin is elevated, says team member Gail Pyne-Geithman, PhD, it
must be exposed to powerful oxidizers that cause the production of
significant amounts of the BOXes. The correlation between elevated
BOXes, bilirubin and oxidative stress in this study, she says, was
"striking."
The researchers point out that although their findings are encouraging
in terms of developing a diagnostic test and treatment, the number of
patients in their study was small and more work is needed to confirm
that vasospasm is more likely to occur in bleeding-stroke patients who
have elevated levels of BOXes.
###
The study is reported in the March 23, 2005 online edition of the
Journal of Cerebral Blood Flow and Metabolism. It was funded by The
National Institutes of Health and The Neuroscience Institute in
Cincinnati. The university, in partnership with the Health Alliance of
Greater Cincinnati, established The Neuroscience Institute in 1998 as
part of an effort to build upon its national reputation for excellence
in neuroscience. The institute includes or is developing research
centers that focus on the main diseases of the brain and nerves such as
stroke, brain tumors, brain trauma, Parkinson's, Alzheimer's, epilepsy,
ALS and multiple sclerosis. Co-authors also include Chad Morgan, MD,
Kenneth Wagner, PhD, Elizabeth Dulaney, Janice Carrozzella, RN, Daniel
Kanter, MD, and Mario Zuccarello, MD.
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