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 tox-ins 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 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 patients 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 online edition of the Journal of Cerebral Blood Flow and Metabolism.
Co-authors include Chad Morgan, MD,
Kenneth Wagner, PhD, Elizabeth Dulaney, Janice Carrozzella, RN, Daniel
Kanter, MD, and Mario Zuccarello, MD.