In tests on rats, researchers at Johns Hopkins and the
University of Michigan have developed a treatment that
helps spinal cord nerves regrow after injury.
The study, whose findings were published in the July
18 issue of the Proceedings of the National Academy of
Sciences, has implications for treating people who may
face amputation of an arm after a violent injury in which
nerves are wrenched from the spinal cord. The new treatment
currently is under study for other types of traumatic
spinal cord injury.
The researchers treated experimental nerve injuries in
rats with an enzyme called sialidase that they isolated
from bacteria. Four weeks later, more than twice as many
nerves in the spinal cords of sialidase-treated rats grew
new nerve fibers compared to untreated rats.
The experimental injury in rats mimicked an injury in
humans that may occur during childbirth or in a motorcycle
accident when an arm is pulled violently away from the
body. This injury causes nerves to be yanked out of the
spinal cord. Without these nerves, the arm loses feeling
and muscle tone. Without muscle tone, the body cannot
support the weight of the arm, and many health problems can
While surgeons can sometimes reattach the nerves to
the spinal cord, this treatment is not as effective as
physicians or patients would like, in part because nerves
in the brain and spinal cord, unlike those in the rest of
the body, fail to grow new nerve fibers. Nerves in the
brain and spinal cord are surrounded by signals from other
cells in the injured area that stop them from growing.
"Molecules in the environment of the injured spinal
cord are specifically instructing the nerve end not to
regrow," said the study's director,
Schnaar, professor of
neuroscience in the Institute of Basic Biomedical
Sciences at Johns Hopkins.
"The brain and spinal cord are extremely crowded with
nerves and nerve fibers, which may be why we have developed
careful controls that tell cells to stop making new
connections," he said. "The crowded central nervous system
has ways to say 'OK, we're done' to keep nerves from
sprouting willy-nilly and making inappropriate connections.
But in gaining the ability to crowd nerves close together,
we have given up flexibility — the ability to heal
"If you sever your finger, it can be surgically
reattached, and nerve fibers typically grow back so that
you can use your finger again," Schnaar said. "In contrast,
the injured brain and spinal cord are rocky terrain for
nerve fiber growth. Finding ways to smooth that road might
help the nerve fibers to regrow."
Several molecules in the spinal cord are known to stop
nerve fibers from growing. Schnaar refers to these
molecules as axon regeneration inhibitors, or simply
"Treatments that eliminate ARIs might allow the nerve
ends to regain their natural regenerative abilities as they
do in the periphery and improve recovery," Schnaar said.
The researchers looked at the boundary between the
spinal cord and the periphery to see if they could coax a
nerve end to grow out of the inhibitory spinal cord into a
more permissive environment that contains fewer ARIs. They
chose to mimic the injury commonly seen in motorcycle
accidents, called brachial plexus avulsion, because it
involves nerves at the boundary between the spinal cord and
In anesthetized rats, the researchers surgically
severed nerves that normally extend from the spinal cord to
the shoulder. They then transplanted a nerve from the hind
leg of the same animal into the spinal cord to reconnect
the injured nerve ends.
To coax the injured nerve ends to grow fibers and
connect to the transplanted nerve, they implanted a pump to
bathe the area with one of three enzymes known to destroy
ARIs. Four weeks after transplantation and enzyme
treatment, the researchers injected dyes into the nerves to
see whether and how many nerve fibers had grown from the
injured cells of the spinal cord into the transplanted
Rats treated with sialidase, one of the three enzymes
tested, showed well over twice the number of new nerve
fibers than rats treated with saline, which is no