X-Message-Number: 13171
Date: Mon, 31 Jan 2000 21:16:09 -0800 (PST)
From: Doug Skrecky <>
Subject: novel use for polyethylene glycol
extropians-digest Monday, January 31 2000 Volume 05 : Number 031
From: Jeff Davis <>
Purdue News
February 2000
Polymer repairs nerve damage
in animals with spinal injuries
WEST LAFAYETTE, Ind. A brief
application of a polymer commonly used in
medicine and cosmetics has been shown to
immediately repair damaged nerve
membranes in live guinea pigs with severe
spinal cord injuries.
The polymer, called polyethylene glycol or
PEG, works by "fusing" the membranes of
damaged nerve cells, and it can be applied
up to eight hours after the injury without
adversely affecting the patient's recovery.
The process may someday be used in
humans with spinal cord injuries to
minimize or reverse the damage to nerve
cells that results in paralysis, says Richard
B. Borgens, professor of developmental
anatomy at Purdue University.
"It's the disruption of the membrane that
leads to the death of the cell," Borgens says.
"In this case, we're talking about a
mechanical injury to nerve cells, which
conduct the impulses needed for movement
and a variety of other functions. If the nerve
cell dies or separates, paralysis will
occur."
Borgens says this is the first study to
demonstrate such a rapid recovery of
function and nerve conduction in the whole
animal with a spinal cord injury.
He and his colleague, Dr. Riyi Shi, both of
Purdue's Center for Paralysis Research in
the School of Veterinary Medicine, report
their findings in the January issue of the
FASEB Journal, a publication of the
Federation of American Societies for
Experimental Biology. A year ago, they
reported similar results in tests conducted
on spinal cords that had been removed from
guinea pigs.
The findings offer the promise of rescuing
substantial portions of damaged spinal cord
at the time of initial surgery, Borgens says.
The researchers plan to move the technique
into clinical testing later this year, using
paraplegic dogs with naturally occurring
injuries.
Because the treatment can be given up to
eight hours after the injury without losing
benefits, PEG may someday be used in
addition to the drug methylprednisolone as
an emergency treatment for spinal cord
injuries, says Borgens.
PEG is a nontoxic, water-soluble polymer
widely used in medicine and cosmetics. In
the study, Borgens and his team applied the
substance across a region of the guinea pig's
crushed spinal cord.
"In most spinal cord injuries in animals and
in people, the spinal cord is not completely
severed, but is more likely to be crushed,"
he says. "It is this crushing or compression
of the spinal cord that causes the nerve
fibers to develop holes in their membranes,
which ultimately leads to cell death and
separation of the nerve fiber within 24 to 72
hours. If the nerve fibers separate, or
otherwise do not conduct impulses,
paralysis will occur."
PEG was applied for two minutes, then
removed. One group of animals received the
application immediately after the injury,
while a second group of animals was
treated with PEG eight hours after the
injury. Following the PEG applications, all
the animals were tested to measure their
ability to conduct nerve impulses through
the spinal cord and to gauge their recovery
of functional behavior.
Nerve impulses through the spinal cord
were measured by stimulating a nerve in the
hind leg and determining whether and when
the impulses arrived at the brain.
Of the 47 guinea pigs used in the study, all
25 of the animals that received PEG were
able to recover some nerve conduction
from 20 percent to 50 percent within 15
minutes after PEG was applied.
Measurements taken days and weeks later
showed that, in addition, the nerve
conduction recovery continued to improve
up to one month after the initial treatment.
Of the 22 animals that did not receive PEG,
not one animal recovered the ability to
conduct nerve impulses through the spinal
cord, Borgens says.
"Amazingly, one hundred percent of the
PEG-treated animals recovered their ability
to conduct nerve impulses, while none of
the control animals did," Borgens says. "By
measuring the quantity of nerve impulses
that travel through the spinal cord, we can
better index the integrity of the spinal cord
after an injury."
To analyze the animals' functional or
behavioral recovery, Borgens and his group
used a measure called "skin rippling," a
behavior found in many animals but not in
humans. Formally called the CTM reflex
for cutaneous trunci muscle reflex the
behavior can be observed as a corrugated
rippling of back skin in response to light
tactile stimulation, for example, when a
cat's back is tickled or when a horse is
assailed by flies.
Borgens says the CTM reflex is an ideal
tool for studying recovery of spinal injuries
because the anatomy of the reflex is well
understood and documented from the
sensation of tickling on the skin to nerve
impulses traveling up the spinal cord, to the
motor nerves and back out to the skin.
"We know all the connections, the complete
circuit, and that's very powerful when
tracking the flow of nerve impulses to see
where they still exist or where they are
blocked," he says. "Also, this is a behavior
that is often permanently lost after severe
spinal injury."
To visualize and measure the CTM
behavior prior to injury, the shaved back of
each sedated guinea pig was touched lightly
with a probe, producing contractions of the
skin. The scientists used markers to indicate
areas on the animals' backs that rippled in
response to the stimulus. In addition, the
process was videotaped to record the
animals' behavior.
The animals were videotaped again after the
injury to show what part of the behavior
was lost. After PEG was applied, the
researchers used a pair of electrodes to
stimulate nerve impulses through the spinal
cord. In animals that showed behavioral
recovery, the researchers compared the new
movements with the videotapes made prior
to the injury to measure the amount of
recovery.
"Only three of the sham-treated animals
recovered some behavioral function after
the injury, but overall they tended to get
worse with time," Borgens says. "Twenty of
the 25 animals treated with PEG recovered
variable amounts of CTM functioning,
which continued to improve with time."
Borgens says the skin rippling test is a more
reliable measure of post-injury behavior
than tests designed to measure walking,
because, unlike people, rats and some other
animals can continue to walk after severe
spinal cord injuries.
"In rats and guinea pigs much of the process
of walking is controlled at a specific
location on the spinal cord, and is less
dependent on nerve impulses traveling to
and from the brain," he says.
Though none of the animals showed a
complete recovery of nerve conduction
function, Borgens says that regaining 20
percent to 50 percent of the function is
significant.
"If you have even 5 percent of the nerve
fibers carrying nerve impulses, you'll get
significantly more than 5 percent back in
terms of restored behavior," he says.
Borgens says the technique may be a
revolutionary new way of dealing with
injuries to the nervous system: "It's too soon
to know whether it would help patients with
old injuries, but it is likely to be useful in
treating recent injuries."
Borgens and Shi plan to conduct clinical
trials in natural cases of paraplegia in dogs
sometime this year. Human clinical trials
are at least two years away.
The research was sponsored by the state of
Indiana, through support of the
Purdue-Indiana University Institute for
Applied Neurology, and through gifts from
Helen Skinner and Mary Hulman George.
Source: Richard Borgens, (765) 494-7600;
Writer: Susan Gaidos, (765) 494-2081;
Purdue News Service: (765) 494-2096;
ABSTRACT
Immediate recovery from spinal cord
injury through molecular repair of nerve
membranes
with polyethylene glycol
Richard B. Borgens and Riyi Shi
A brief application of the hydrophilic
polymer polyethylene glycol (PEG) swiftly
repairs nerve membrane damage associated
with severe spinal cord injury in adult
guinea pigs. A two-minute application of
PEG to a standardized compression injury
to the cord immediately reversed the loss of
nerve impulse conduction through the injury
in all treated animals while nerve impulse
conduction remained absent in all
sham-treated guinea pigs. Physiological
recovery was associated with a significant
recovery of a quantifiable spinal
cord-dependent behavior in only
PEG-treated animals. The application of
PEG could be delayed for up to eight hours
without adversely affecting physiological
and behavioral recovery, which continued
to improve for up to one month after PEG
treatment.
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