Scientists Help Nerve Fibers To Regrow After Spinal Cord Injury

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Scientists Help Nerve Fibers To Regrow After Spinal Cord Injury

http://www.medicalnewstoday.com/medicalnews.php?newsid=47568

In tests on rats, researchers at s Hopkins and the University of

Michigan have developed a treatment that helps spinal cord nerves

regrow after injury. The findings will be published in the July 18

issue of the Proceedings of the National Academy of Sciences. The

study 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 motorcycle accidents 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 develop.

While surgeons can sometimes reattach the yanked nerves to the spinal

cord, this treatment is not as effective as physicians or patients

would like. This is 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, " says the

study's director, Schnaar, Ph.D., professor of pharmacology

and neuroscience in the Institute of Basic Biomedical Sciences at

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. 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 after injury. "

" If you sever your finger, it can be surgically reattached, and nerve

fibers typically grow back so that you can use your finger again, "

says Schnaar. " In contrast, the injured brain and spinal cord are

rocky terrain for nerve fiber growth, " he says. " 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 ARIs.

" Treatments that eliminate ARIs might allow the nerve ends to regain

their natural regenerative abilities as they do in the periphery and

improve recovery, " says Schnaar.

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

periphery.

The researchers surgically severed nerves that normally extend from

the spinal cord to the shoulder of anesthetized rats. 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 used an implanted pump to bathe the area

with one of three different 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 grew

from the injured cells of the spinal cord into the transplanted

nerve.

Rats treated with one of the three enzymes tested, sialidase, showed

well over twice the number of new nerve fibers than rats treated with

saline, which is not expected to enhance nerve growth. Moreover, the

researchers saw that the new fibers were made by nerve cells residing

in the spinal cord.

" We have established that the enzyme sialidase, which destroys one of

the molecules that inhibits nerve regeneration, is sufficient to

robustly improve nerve fiber outgrowth from the spinal cord, " says

Schnaar.

Surgical transplantation of a peripheral nerve to help nerve fiber

growth from the spinal cord has shown limited success in humans. " The

addition of a new treatment to enhance our current surgical

management of brachial plexus avulsion in people would be welcomed by

patients and surgeons alike " says Lynda Yang, M.D., Ph.D., an

assistant professor of Neurosurgery at the University of Michigan.

Dr. Yang, the study's lead author, helped pioneer the study of ARIs

while a doctoral student with Dr. Schnaar at s Hopkins in the

1990s.

Having shown here that sialidase can increase the number of spinal

cord nerve cells that extend fibers into a transplanted nerve, Dr.

Yang now is testing if the nerves re-establish muscle control. " We're

very interested in seeing how much function you can get back, " she

says.

According to Schnaar, there is some evidence that this transplant

technique coupled with sialidase treatment can coax other, nearby

nerve cells within the spinal cord to grow out as well. " Once you

rewire, then the brain does an amazing job of sorting it all out, " he

says.

Having established the ability of sialidase to improve spinal nerve

regeneration into transplanted peripheral nerves, Schnaar and his

research team at Hopkins are testing the same treatment to see

whether it will help nerve regeneration in other types of spinal cord

injuries.

" Even a small improvement might mean a lot. People with spinal cord

injuries generally are not looking to play football, " says

Schnaar, " but to regain basic functions. A modest improvement in

nerve regeneration might make a big improvement in a patient's

quality of life. "