Getting on your nerves: $1.4 million NIH grant to study the regeneration of nerves

November 09, 2011

Injuries to the nervous system affect large numbers of people globally. Such injuries can result in loss of feeling or movement. With a new $1.4 million grant from the National Institutes of Health, Deanna Thompson, associate professor of biomedical engineering at Rensselaer Polytechnic Institute, will investigate a promising new method to heal traumatic nerve damage, using electrical stimulation to prime and pump neuronal growth.

The grant, titled "Directed Formation of Enhanced 3-dimensional oriented Schwann Cellular Arrays for the Repair of Large-Gap Peripheral Nerve Injuries," will span a four-year period.

The research looks specifically at healing the peripheral nervous system, which is the system of nerves outside of the brain and spinal cord that extends throughout the rest of our body. The system has a greater ability to repair itself compared to the central nervous system housed in the brain and spinal cord, but patients with severe injuries to the peripheral nervous system rarely regain full function.

Thompson and her colleagues will further pursue some promising discoveries that they have already made on how nerve repair can be stimulated and directed to repair large-gap injuries that cannot spontaneously regenerate.

By using small electrical pulses, similar to the electrical stimulation created naturally in the body during development, Thompson has found that she can orient and direct helper cells called Schwann cells into the site of an injury. In addition, she has found that the pulses also stimulate re-growing nerves to extend faster, potentially increasing the rate of repair.

Thompson wants to see the effective tools used for bone and wound healing one day applied to restore nerve function following trauma.

"Doctors currently use electrical stimulation technologies to heal a variety of injuries to bone or muscle as well as to manage pain, heal diabetic wounds, and deep brain stimulation," Thompson said. "These stimulators have not yet been widely applied to treat nerve injuries. Using this funding, we hope to explore the idea of using electrical stimulation to both fuel and provide a directional cue for nerve repair by guiding and enhancing these helper cells, which are a known rate-limiting factor in peripheral nerve injury."

Nerves within the human body are similar to the reams of wire that run through our homes and offices. They transmit signals. They are insulated to protect and efficiently direct these signals. And when they are severed, the connection is lost and communication is immediately halted at both ends. But, unlike an electrical wire, the dynamic nervous system can work to repair itself.

When a nerve in the peripheral nervous system is severed, the growing portion of the regenerating nerve is called the axon and the axon needs to navigate through the injury site and reconnect to its target. To aid this re-growth, Schwann cells sprout from both broken ends of the severed nerve. Like microscopic electricians, the Schwann cells begin to stretch their way across the gap to mend the connection. As they go, they emit important growth factors that invigorate cell growth. These growth factors help call in and direct the new nerve cells to the injury. It is this repopulation of the injury with new cells that is often the log jam to complete reconnection of broken nerves, particularly in cases where the gap in a severed nerve is large, said Thompson.

Schwann cells can be so exceptional at directing the new cells that they rush to send out growth factors and too few of them make it all the way to the injury site or gap. In these cases, the axons do not receive the proper support and never make it to their final destination. The reconnection is never made and function is not restored.

By stimulating the growth of both the axons and the Schwann cells, Thompson hopes to prevent these neuronal roadblocks by directing the Schwann cells and repopulating the injury site in addition to stimulating faster axon re-growth. The new grant will give her the opportunity to further investigate the mechanisms she has uncovered that align the Schwann cells and increase the neuron growth.

"If we are able to direct neuron and Schwann cells, it is possible that other types of nerve cells such as those found in the spinal cord or brain might also be responsive to this," Thompson said of the potential future impact of the work.
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Thompson is collaborating on the research with Lee Ligon and Sheppard Salon of Rensselaer; Sally Temple of New York Neural Stem Cell Institute, and Vivian Mushahwar of the University of Alberta.

Rensselaer Polytechnic Institute

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