Growth Factors Improve Accuracy Of Regenerating Nerve Cells

April 29, 1996

SAN DIEGO -- Researchers at Duke University Medical Center have demonstrated that the addition of two naturally occurring growth factors significantly improved the ability of severed nerve fibers to reconnect with a high degree of accuracy.

The Duke studies, carried out in rats, could lead to new strategies to improve the effectiveness of peripheral nerve repair procedures in humans, researchers said. Peripheral nerves arise from the central nervous system, such as the spinal cord, and carry impulses to the rest of the body.

The results of the study were presented Tuesday at the annual meeting of the Society for Neuroscience by Dr. Roger Madison, associate professor of neurosurgery and neurobiology. Madison's research is supported by the National Institutes of Health and the Department of Veterans Affairs.

Nerves are much like coaxial cables -- enclosing thousands of sensory and motor axons within a protective sheath. Axons are long fibers that conduct nerve impulses. When a nerve is severed, regrowing axons must find their counterparts and connect for orderly function to return.

"When the two growth factors were added to the nerve guide, the accuracy of the regenerating motor axons reconnecting to muscle increased dramatically, from 51 percent to 90 percent," Madison said. "For sensory axons, the rate increased from 59 percent to 69 percent, an increase, but one not deemed to be statistically significant."

Reconnection is vital because, once severed, that part of the nerve most distant from the spinal cord begins to degenerate, eventually leading to the loss of sensation and the ability to move the muscles to which the nerves are connected.

Standard nerve regeneration therapy in people usually involves directly reconnecting the nerve, if possible, or taking a portion of a nerve from another part of the body to make the reconnection. More than 200,000 of these procedures are performed each year in the United States. However, these procedures have had limited success.

"Studies in humans have shown that less than 3 percent of the patients who have these procedures performed on nerves of the wrist recover normal sensation after five years," Madison said. "Less than 25 percent of the patients fully recover motor function."

The disappointing results to date have spurred researchers to seek alternative nerve repair strategies. For more than 10 years, Madison and his colleagues have been using animal models to test different types of tubes, which when attached to the ends of severed nerves act as a guide for the regenerating axons.

In the current study, Madison has found that the addition of two different growth factors -- acidic fibroblast growth factor (aFGF) and nerve growth factor (NGF) -- significantly improved the ability of regenerating axons not only to grow through the guide tube but to reconnect to the appropriate targets with greater accuracy.

These growth factors are produced normally within the body in small amounts -- the Duke researchers use highly purified forms of these growth factors in their experiments.

The experiment involved 27 animals -- 10 served as controls, 10 others had a nerve gap of 4mm repaired only with the nerve guides, and seven had the nerve guides filled with the two growth factors. After four weeks, flourescent tracers were added to the site of repair to determine the extent of axonal regrowth and to what degree motor axons reconnected to muscle versus inappropriately growing to skin.

Madison said that the increased accuracy is most likely due to the fact that the growth factors stimulated the spouting of more axons from the site of injury. With this increased amount of axonal branching, the relative likelihood of an axon finding its appropriate target increased.

"If we did nothing at all except use the nerve guide, we would expect about half of the axons to find the right connection," Madison said. "With the growth factors, more than 90 percent got back. That is a very profound effect."

Another factor, according to Madison, is that when these growth factors are added to the site of injury, their concentration is much higher than the amount that would normally be present at the site. The nerve tube keeps the growth factors in constant contact with the nerves and not diluted throughout the body.

Madison's colleagues on this project were Duke's Victor Wang and Simon Archibald in Duke's division of neurosurgery.
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Duke University

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