In a new mouse study, a team of researchers from UCLA, the Swiss Federal Institute of Technology, and Harvard University have discovered a key element in restoring functional activity after spinal cord injury. Neuroscientists' research shows that growing specific neurons back into their natural target areas leads to recovery, while random regeneration has no effect.
In a 2018 study published in Nature, the team identified a treatment that triggers axons (tiny fibers that connect nerve cells and enable communication) to regrow after spinal cord injuries in rodents. However, even if this approach succeeds in regenerating axons from severely injured spinal cord, achieving functional recovery remains a significant challenge.
In the new study, published in the journal Science, researchers aimed to determine whether directing the regeneration of axons in specific subsets of neurons to their native target areas could lead to meaningful functional recovery after spinal cord injury in mice. They first used advanced genetic analysis methods to identify a population of nerve cells that can improve walking after partial spinal cord injury.
The researchers then found that simply regenerating axons from these nerve cells through the lesioned area of the spinal cord without specific guidance had no impact on functional recovery. However, when the researchers refined this strategy and used chemical signals to attract and guide the regeneration of these axons to their natural target areas in the lumbar spinal cord, significant improvements in walking ability were observed in a mouse model of complete spinal cord injury.
"Our study provides important insights into the complexity of axonal regeneration and the requirements for functional recovery after spinal cord injury," said Michael Sofroniew, MD, senior author of the new study and professor of neurobiology at the David Geffen School of Medicine at UCLA. "This study highlights the need not only to allow axons to regenerate at the site of the lesion, but also to actively guide axons to their natural target areas to achieve meaningful neurological recovery."
Understanding how to re-establish the projections of specific neuronal subpopulations to their native targets holds significant promise for the development of therapies aimed at restoring neurological function in large animals and humans, the researchers say. However, the researchers also acknowledge that promoting long-distance regeneration in non-rodent animals is complex and requires strategies with complex spatial and temporal characteristics.
Nonetheless, they concluded that applying the principles presented in their work "will open the framework to achieve meaningful spinal cord repair after injury and potentially accelerate repair after other forms of central nervous system injury and disease."