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
"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," said lead researcher
Sylvain Dore (doh-ray), 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 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 to have a protective effect
against inflammation in animal models.
Dore 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
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 and (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," Dore said.
Roughly 700,000 people experience a stroke each year
in the United States. Of those, 87
percent have an ischemic stroke, 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
Dore 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 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," Dore said. "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.
Additional researchers, all from Johns Hopkins, are
Sofiyan Saleem and Hean Zhuang, both of
the Department of Anesthesiology and Critical Care
Medicine, and Shyam Biswal, of the Department
of Environmental Health Sciences.