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Ed. Note: The following is a press
release from Purdue University.
WEST LAFAYETTE,
Ind., June 21 (AScribe Newswire) -- Purdue University researchers may have
isolated the substance most responsible for the tissue damage that follows
initial spinal cord injury, a discovery that could also improve treatments
for a host of other neurodegenerative conditions.
A research team led by Riyi Shi (REE-yee SHEE) has found that a chemical
called acrolein, a known carcinogen, is present at high levels in spinal
tissue for several days after a traumatic injury. Although acrolein is
produced by the body and is non-toxic at normally occurring low levels, it
becomes hazardous when its concentration increases, as it often does in
tissue that experiences stresses such as exposure to smoke or pesticides.
That list of stresses now includes physical damage, and in the case of
spinal injury, acrolein's hazard may be the key in causing debilitating
paralysis that sets in after the initial trauma.
"When a spinal cord ruptures, not only are the traumatized cells at
increased risk of damage from free radicals that oxidize the tissue, but the
cells also spill chemicals that actually help the free radicals to launch
repeated attacks," said Shi, who is an associate professor of neuroscience
and biomedical engineering in Purdue's School of Veterinary Medicine and
Weldon School of Biomedical Engineering. "Our latest research indicates that
acrolein may be the primary culprit that enables this vicious cycle. Because
acrolein has already been implicated in cancer and neurological diseases,
drugs that detoxify it could become important for treating not only spinal
cord damage but a host of other conditions as well."
The research, which Shi carried out with his student Jian Luo and Koji
Uchida of Japan's Nagoya University, appears in the now-available March 2005
issue of the scientific journal Neurochemical Research.
Free radical molecules are well-known enemies of bodily health, and for
years, physicians have recommended a diet rich in antioxidants - such as
vitamins C and E - which are able to attach themselves to free radicals,
detoxifying them. While there is nothing inherently wrong with this
approach, Shi said, it might not be getting at the root of some health
problems.
"Antioxidants are good scavengers of free radicals, and it's certainly wise
to have plenty of them circulating in your bloodstream," he said. "The
trouble is that when free radicals start attacking tissue, it happens in a
tiny fraction of a second, after which they are gone. But the acrolein that
these attacks release survives in our bodies much longer, for several days
at least, and its toxicity is well documented."
For example, acrolein has long been known to cause cancer when its
concentration in the body rises, and not much is needed to be dangerous.
When a person inhales smog or tobacco smoke, for example, the fluids lining
the respiratory tract show an acrolein concentration of about a millimole -
not much by measuring-cup standards, but still over 1,000 times more than
usual.
"If you took a single grain of salt from a shaker and dissolved it in a
liter jug, the water wouldn't taste very salty," Shi said. "But even that
would be more than a millimole, and that's much more acrolein than the body
can handle at once."
Because a high concentration of acrolein also has been linked to
neurodegenerative conditions such as Parkinson's, Huntington's and
Alzheimer's diseases - all of which progress slowly and resist treatment -
Shi's team decided to see if the chemical was present in another
slow-developing, seemingly untreatable condition: the degeneration of the
spinal cord after initial traumatic injury.
"Unlike most other parts of the body, spinal cord tissue does not heal after
injury," Shi said. "After the initial shock, it actually gets worse. Science
has long been aware that some chemicals the damaged cells release are part
of the problem, but no one has ever been sure which chemicals are
responsible."
When a spine is damaged, the change in its ability to function follows a
well-defined pattern. In response to the initial shock, the spine
immediately becomes completely nonfunctional but then starts to recover
quickly. Over the course of the next few days, in response to the secondary
damage, the spine's function again begins to drop, and within about three
days it has leveled off at a point of near non-functionality.
"What our group did was measure the levels of acrolein in the injured spines
of 25 guinea pigs for several days following an injury," Shi said. "We found
that levels of acrolein peak 24 hours afterward, and they remain high for at
least a week. Because acrolein has such a long lifespan and is so toxic, we
theorize that it is primarily responsible for the secondary damage that
keeps injured spines from healing."
Acrolein's involvement with other conditions suggests that it could be the
key to fighting a number of diseases, Shi said.
"When the brain suffers a stroke, for example, it is deprived of oxygen,
which is often thought to be the cause of brain damage. But, in fact, you
can starve the nervous tissue of oxygen for up to an hour without harm if
only you control the acrolein levels," Shi said. "This paper suggests that
the body is generally pretty resilient but that acrolein may be something it
can't handle."
Shi said that some drugs already under development for other conditions
could be used to treat neurodegenerative diseases as well.
"Hypertension drugs, which bind to acrolein and detoxify it, are already
under study for their added potential to promote liver health," Shi said.
"We would like to see whether they also could be modified to treat the
conditions we are interested in."
Further research will be necessary to determine how great a role acrolein
actually plays in the process of secondary spinal cord damage, but Shi said
that once this role is clarified, drugs that counter acrolein's effects
could join the other approaches to treating spinal cord injury under
development at Purdue's Center for Paralysis Research.
"My colleague Richard Borgens and I have already had our hands in developing
PEG, a substance that coats damaged spinal cells so that their membranes can
heal and also oscillating field stimulator implants that encourage the
tissue to regenerate," Shi said. "We are hopeful that detoxifying acrolein
will allow doctors to stop the chemical attack cycle as well, adding to the
number of treatment methods available."
The center was established in 1987 both to develop and to test promising
methods of treatment for spinal cord injuries. The center uses its close
affiliation with the Department of Veterinary Clinical Sciences in the
College of Veterinary Medicine to move basic laboratory methods into
clinically meaningful veterinary testing.
This research was funded in part by the National Institutes of Health and
the State of Indiana.
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RELATED WEB SITES:
Purdue Center for Paralysis Research:
http://www.vet.purdue.edu/cpr/
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