ScienceDaily (Oct. 10, 2008) —
Working with genetically engineered mice, researchers at Johns Hopkins
have shown that daily doses of a standardized extract from the leaves of
the ginkgo tree can prevent or reduce brain damage after an induced
stroke.
The scientists, in a report published in Stroke, say their work lends
support to other evidence that ginkgo biloba triggers a cascade of
events that neutralizes free radicals known to cause cell death.
"It's still a large leap from rodent brains to human brains but these
results strongly suggest that further research into the protective
effects of ginkgo is warranted," says lead researcher Sylvain Doré,
Ph.D., an associate professor in the Department of Anesthesiology and
Critical Care Medicine. "If further work confirms what we've seen, we
could theoretically recommend a daily regimen of ginkgo to people at
high risk of stroke as a preventive measure against brain damage."
In the study, researchers gave ginkgo biloba EGb 761 - a lab-quality
form of the extract - to normal mice and HO-1 knockout mice, mice
lacking the gene that produces the enzyme heme oxygenase-1(HO-1). HO-1
breaks down heme, a common iron molecule found in blood, into carbon
monoxide, iron and biliverdin. HO-1 has been shown to act as an
antioxidant and have a protective effect against inflammation in animal
models.
Doré and his team gave 100 milligrams per kilogram of EGb 761 extract
orally once daily for seven days before inducing stroke in the mice by
briefly blocking an artery to one side of the brain.
After stroke induction, the mice were tested for brain function and
brain damage. One such test, for example, involves running patterns,
another tests reaction to an external stimulus. Similar tests were
conducted on mice that did not receive the ginkgo extract.
Neurobehavioral function was evaluated before the study and at 1, 2
and 22 hours after stroke using a four-point scale: (1) no deficit, (2)
forelimb weakness, (3) inability to bear weight on the affected side,
(4) no spontaneous motor activity.
Results showed that normal mice that were pretreated had 50.9 percent
less neurological dysfunction and 48.2 percent smaller areas of brain
damage than untreated mice. These positive effects did not exist in the
HO-1 knockout mice.
"Our results suggest that some element or elements in ginkgo actually
protect brain cells during stroke," says Doré.
Roughly 700,000 people experience a stroke in the United States
annually. Of those, 87 percent have an ischemic stroke, which is caused
by a blocked artery in the brain. Some brain damage occurs simply from
the lack of blood getting to brain cells; however, it is known that an
increase in the presence of free radicals at the site of an ischemic
stroke - once the clot is cleared and the blood supply returns - is also
a major cause of resulting brain cell damage. Free radicals are toxic
oxygen molecules that are produced when cells die. According to Doré and
his team, ginkgo increases HO-1 levels, and the antioxidant properties
of this enzyme eliminate free radicals at the surrounding regions of the
stroke site.
The only current treatment for ischemic stroke is to clear the clot
with tissue plasminogen activator (tPA) or other means. This, however,
offers no real protection against the cell damage that occurs when blood
flow is restored.
"Ginkgo has long been touted for its positive effects on the brain
and is even prescribed in Europe and Asia for memory loss," says Doré.
"Now we have a possible understanding for how ginkgo actually works to
protect neurons from damage."
Native to China, the ginkgo tree is grown as an ornamental shade tree
in Australia, Southeast Asia, Europe, Japan and North America. It is
commercially cultivated in France and the United States. It has a grey
bark, reaches a height of 35 meters and a diameter of 3 to 4 meters. It
has deciduous, fan-like leaves that are green, grey-yellow, brown or
blackish.
Additional researchers include Sofiyan Saleem, Ph.D., and Hean Zhuang,
M.D., of the Department of Anesthesiology and Critical Care Medicine,
and Shyam Biswal, Ph.D., of the Department of Environmental Health
Sciences, all from Johns Hopkins.
