Researchers at Johns Hopkins have shown that brain
damage was reduced by as much as 62.2
percent in mice who inhaled low amounts of carbon monoxide,
or CO, after an induced stroke.
The scientists, in a report published online today,
Dec. 15, in Neurotoxicity Research, say that
although carbon monoxide gas has a long reputation as an
odorless, colorless cause of organ damage
and even death, there is now evidence that it can protect
nerve cells from damage.
"CO is made naturally by the body and can serve a
protective function under various
circumstances," said lead author Sylvain Dore (doh-ray), an
associate professor in the
Department of
Anesthesiology and Critical Care Medicine at the School
of Medicine. "The idea for our experiment
was to see if external CO could have a similar effect."
Some of the brain damage associated with stroke
results directly from a cutoff in blood supply
to nerve cells, but a good deal of the injury is due to
chemical reactions and the resulting release of
tissue-damaging free radicals when blood flow is restored.
Currently the only treatment for such
strokes is to clear out the blood clot with clot busters,
such as tissue plasminogen activator or other
means, but these offer no protection from so-called
"reperfusion" damage.
Dore and his team induced stroke in the mice by
briefly blocking an artery to one side of the
brain. Afterward, the mice were exposed to either 125
parts-per-million or 250 ppm of CO. A control
group was exposed only to air. Each was tested for physical
brain damage and function, mainly by
observing running patterns and reactions to certain
stimuli.
Results showed that mice exposed only to air had brain
damage to 49.9 percent of the side of
the brain where the blood supply was cut off. In mice that
inhaled 125 ppm of CO immediately after
stroke, brain damage dropped to 33.9 percent, and in mice
getting 250 ppm, CO damage fell to 18.8
percent. Neurological function test scores were also
significantly improved for mice that received CO
after stroke.
Dore and his team say the results were almost the same
for mice who were treated as long as
one hour after stroke, and results even looked good with
mice treated three hours after stroke.
"It is important that we still see CO's
neuroprotection at one and three hours since many stroke
victims will not receive immediate treatment," Dore
said.
Dore and his team speculate that CO's protective
effects might be due to its ability to dilate or
open blood vessels, therefore increasing blood flow; its
anti-inflammatory properties, preventing cell
death caused by inflammation; and its capacity to reduce
water in the brain. Excessive water in the
brain increases intracranial pressure, which kills brain
cells.
Dore says future research will focus on finding the
lowest possible effective therapeutic dose
of CO that protects against stroke damage in order to limit
CO toxicity that is known to occur at
higher doses.
Roughly 700,000 people experience a stroke in the
United States annually. Of those, 87
percent suffer ischemic stroke, which is caused by a
blocked artery in the brain.
Emil Zeynalov, of the Department of Anesthesiology and
Critical Care Medicine at the School of
Medicine, also contributed to this research.
This research was supported by the National Institutes
of Health.
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