Previously injured axons (red) can grow through a dense astrocyte scar (green) in the presence of molecules that stimulate growth (blue).
According to a new mouse study, astrocyte scars—long considered responsible for blocking neuronal regrowth across the level of spinal cord injury—may actually be required for repair and regrowth following spinal cord injury. The research was funded by the US National Institutes of Health (NIH), and published in Nature.
“At first, we were completely surprised when our early studies revealed that blocking scar formation after injury resulted in worse outcomes. Once we began looking specifically at regrowth, though, we became convinced that scars may actually be beneficial,” says Michael V Sofroniew, professor of neurobiology at the University of California (Los Angeles, USA) and senior author of the study. “Our results suggest that scars may be a bridge and not a barrier towards developing better treatments for paralysing spinal cord injuries.”
Using three different mouse models to examine the effect of astrocyte scars on axonal regrowth, Sofroniew’s team was able to remove the scars or prevent them from forming after a spinal cord injury. The results revealed that without astrocyte scars, there was no regrowth.
In another experiment of spinal cord injury in mice, Sofroniew’s team shuttled growth factors, specific molecules that stimulate axons to grow, to the injury site and discovered that there was robust regrowth through astrocyte scars. However, if the researchers prevented scar formation, the regrowth was significantly reduced.
Genetic analyses revealed that astrocytes as well as non-astrocyte cells released a variety of chemicals involved in regrowth at the injury site. In this mix, Sofroniew and his colleagues found molecules that block regrowth along with molecules that support it.
“This…research provides further evidence about the complexity of the brain and spinal cord’s injury response. It shows that scar forming astrocytes support axon growth and suggests that therapeutics directed only at blocking these cells may not enhance regeneration of the injured spinal cord,” says Lyn Jakeman, program director at the NIH’s National Institute of Neurological Disorders and Stroke (NINDS), which provided funding for the study.
Sofroniew and his colleagues are planning to investigate the exact mechanisms by which astrocytic scars support growth and ways to increase that response. “These preliminary findings established that axonal growth can occur in the presence of scars in mice. Eventually, we would like to see the regenerating axons grow far enough into healthy tissue to establish functional connections,” says Sofroniew.