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Anti-scar agent may be key to nerve regeneration

by Anissa Anderson Orr

Stephen Davies, PhD

Infusing a naturally occurring anti-scarring agent called decorin into the damaged spinal cords of rats suppresses key molecules that block nerve regeneration after spinal cord injury, said Baylor College of Medicine researchers in a study published in a recent issue of the European Journal of Neuroscience.

The researchers are the first to use decorin in this manner. Decorin derives its name from its appearance in pictures from electron microscopes. It shows up on the collagen network, decorating the collagen fibers.

“Scar tissue that develops at sites of injury stops the regeneration of connections in the adult central nervous system,” said Stephen Davies, PhD, lead author on the study and an assistant professor of neurosurgery and neurosciences at BCM. “Infusion of decorin into spinal cord injuries prevents the formation of proteoglycan-rich scar tissue by suppressing inflammation.”

Misaligned scar tissue that forms at spinal cord injuries physically blocks nerve regeneration. This scar tissue contains molecules called chondroitin sulfate proteoglycans that inhibit nerve fiber growth.

Decorin hinders the action of molecules that promote inflammation, which means that the immune system is responding to an invasion. When a spinal cord injury occurs, these molecules called transforming growth factors are produced. They are thought to promote the formation of scar tissue.

In this study, Davies and his colleagues infused decorin directly into the injury site in rats. To do this, they used a mini-pump system with silica cannulas or tiny tubes 160 microns (1 millionth of a meter) in diameter. The tiny cannulas did not contribute to the formation of scar tissue as bigger tubes would.

Viewing the site of the injury with the help of a high-powered laser scanning microscope and the using protein chemistry to analyze tissue samples, Davies and his co-workers showed that infusion of decorin reduced inflammation, scar formation and the levels of some proteoglycans by as much as 80 to 95 percent. This made it possible for the nerve fibers called axons to grow across spinal cord injuries in just four days.

“We have found a promising new approach to controlling inflammation and scar formation, which will be an important part of future strategies to encourage axon regeneration and recovery after spinal cord injury,” Davies said.

The work was supported by The Institute for Rehabilitation and Research Foundation’s Mission Connect and conducted in collaboration with scientists at Integra LifeSciences Holdings Corporation, The Burnham Institute and GTC Biotherapeutics Inc, who together developed the genetically engineered form of human decorin for use in the study.

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