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.

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