In a study on mice, a group of researchers identified a crucial element for recovering functional activity following spinal cord injury.
The neuroscientists showed that recovery occurred only when specific neurons were grown back to their regular target locations; random regrowth did not.
In a 2018 publication published in Nature, the researchers identified a treatment strategy that induces axons, the tiny threads that connect nerve cells and permit them to communicate, to sprout following spinal cord injury in mice. Although that approach proved effective in rebuilding axons across severe spinal cord lesions, functional recovery remained a significant obstacle.
The researchers intended to investigate if directing the regeneration of axons from certain neuronal subpopulations to their native target regions in mice would result in meaningful functional restoration.
They started by applying advanced genetic research to find nerve cell clusters that improve walking after a partial spinal cord injury.
The researchers discovered that just regenerating axons from these damaged nerve cells across the spinal cord had no effect on functional recovery.
Significant gains in walking ability were reported in a mouse model of total spinal cord injury when the technique was refined to include the use of chemical signals to attract and guide the regeneration of these axons to their natural target site in the lumbar spinal cord.
"Our study provides crucial insights into the intricacies of axon regeneration and requirements for functional recovery after spinal cord injuries,” said Michael Sofroniew, MD, PhD, professor of neurobiology at the David Geffen School of Medicine at UCLA and a senior author of the new study.
“It highlights the necessity of not only regenerating axons across lesions but also of actively guiding them to reach their natural target regions to achieve meaningful neurological restoration."
The authors say understanding that re-establishing the projections of specific neuronal subpopulations to their natural target regions holds significant promise for the development of therapies aimed at restoring neurological functions in larger animals and humans. However, the researchers also acknowledge the complexity of promoting regeneration over longer distances in non-rodents, necessitating strategies with intricate spatial and temporal features.
Still, they conclude that applying the principles laid out in their work “will unlock the framework to achieve meaningful repair of the injured spinal cord and may expedite repair after other forms of central nervous system injury and disease.”
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