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Spinal Cord Axon Injury Location Determines Neuron’s Regenerative Fate

Shepherd Center director of spinal cord injury research comments on UC San Diego study.

Researchers have reported a previously unappreciated phenomenon in which the location of injury to an axon – a neuron’s communication wire in the spinal cord – determines whether the neuron simply stabilizes or attempts to regenerate. The study, published April 30 in the research journal Neuron, demonstrates how advances in live-imaging techniques are revealing new insights into the body’s ability to respond to spinal cord injuries (SCI).

While the body of a neuron is small, its axon can extend far up or down the spinal cord, which is about one and half feet long in humans. Along that distance, the axon branches out to make hundreds of connections with other cells, sending out signals that allow us to sense and respond to the world around us – unless something happens to disrupt the axon’s reach, that is. Adult human axons in the brain and spinal cord are very limited in their ability to regenerate after injury – a hurdle that researchers are trying to overcome in the treatment of SCI and neurodegenerative diseases of the brain.

In the study reported in Neuron, researchers at University of California, San Diego School of Medicine, senior author and associate professor of neurosciences Binhai Zheng, Ph.D., first author Ariana O. Lorenzana, Ph.D., and colleagues used a sophisticated optical imaging technique that allowed them to directly visualize the spinal cord in living mouse models. With this approach, the researchers systematically examined the effects of axon injury location on degeneration and regeneration of the injured branch. The injury locations they compared were just before an axon’s major branch point (where a single axon branches into two) and just after it. The injuries just after the branch point cut off one branch, leaving the other intact, or cut both branches.

The researchers found that injury to the main axon, before a branch point, resulted in regeneration in 89 percent of the cases. Axons with both branches cut after a branch point regenerated in 67 percent of cases. Regeneration occurred in the form of axon elongation, branching or both for at least five days after injury. In contrast, regeneration occurred in only 12 percent of cases following cuts to just one of two axon branches after a major branch point. In this case, the injured branch trims itself all the way back to the base, preserving the function of the other, uninjured branch.

“We think that if an axon is injured in such a way that it still has some kind of connection, is still transmitting signals, the neuron can justify stabilization, but not the energy it would take to either regenerate axon length or just kill the whole thing off,” Dr. Zheng said. “On the other hand, once both branches of an axon are cut and there’s no longer any connection or output, the neuron can justify the energy and resources to regenerate, even though that effort is largely futile in the central nervous system of an adult mammal.”

This is a new, yet very fundamental, understanding of neuron behavior – one that will be important to keep in mind as new therapeutic approaches are proposed for spinal cord injuries, the researchers said.

“In mammals, the nervous system has many obstacles to axon regeneration, including both factors that inhibit growth and factors that inhibit the factors that promote growth,” said Edelle Field-Foté, Ph.D., PT, director of spinal cord injury research at Shepherd Center in Atlanta. “The science underlying the study may have relevance to humans with SCI in the future if scientists are able to determine why some areas of the axon are more likely to regenerate. For this work to be of clinical value (for treatment in humans), scientists would first need to understand what it is about properties of the axon before the major branch point that allowed it to have greater regeneration, compared to the properties of the axon branches that had less regeneration.”

The co-authors of the UC San Diego study are Jae K. Lee, Matthew Mui, and Amy Chang. The research was funded, in part, by the National Institutes of Health, Dana Foundation and Roman Reed Foundation.

About Shepherd Center

Shepherd Center provides world-class clinical care, research, and family support for people experiencing the most complex conditions, including spinal cord and brain injuries, multi-trauma, traumatic amputations, stroke, multiple sclerosis, and pain. An elite center recognized as both Spinal Cord Injury and Traumatic Brain Injury Model Systems, Shepherd Center is ranked by U.S. News as one of the nation’s top hospitals for rehabilitation. Shepherd Center treats thousands of patients annually with unmatched expertise and unwavering compassion to help them begin again.