For many years, researchers have thought that the scar that forms after a spinal cord injury actively prevents damaged neurons from regrowing. In a study of rodents, scientists supported by the National Institutes of Health showed they could overcome this barrier and reconnect severed spinal cord nerves by turning back the neurons’ clocks to put them into an early growth state. Once this occurs, neurons could be induced to regrow across the scarred tissue. The research was supported by the National Institute of Neurological Disorders and Stroke (NINDS), part of NIH.
“For decades researchers have been trying to make severed neurons regrow across a spinal cord injury and reconnect with neurons on the other side. This study suggests that may require manipulating three key growth processes,” said Lyn Jakeman, Ph.D., program director, NINDS. “These insights are important for understanding the mechanisms of injury and regeneration that may one day be applied to develop potential treatments for spinal cord injury.”
Neurons send signals to each other through long projections called axons. When the spinal cord is injured, many of these axons are severed, leading to a loss of sensation and/or paralysis below the injury site. In response, a scar forms within the damaged tissue, and while the axons may briefly attempt to regrow, this process is unsuccessful. Because these connections between neurons are made initially as the body is developing, researchers have sought to restore those developmental conditions to potentially help the damaged cord heal.
“There are several growth patterns in the spinal cord that shut down after development,” said Michael V. Sofroniew, M.D., Ph.D., professor at the Brain Research Institute at UCLA and senior author of the study published in Nature. “We wanted to see if we could reactivate those patterns following injury and whether that would lead to regrowth of the axons.”
Using both mouse and rat spinal cord injury models, the researchers from UCLA and their collaborators at Harvard Medical School, Boston, and the Swiss Federal Institute of Technology, Lausanne, Switzerland, looked at three components of the regrowth process.
First, they tried to genetically turn back the neurons’ clock by reactivating the growth program that produced the original connections, specifically neurons that look like they are trying to regrow. While not active in adults, the neurons still carry the program used during early growth. By injecting viruses containing genes related to this program, the researchers were able to revert spinal cord neurons back to a state where axon growth could occur.