Reducing Pericyte-Derived Scarring Promotes Recovery after Spinal Cord Injury

CNS injury often severs axons. Scar tissue that forms locally at the lesion site is thought to block axonal regeneration, resulting in permanent functional deficits. We report that inhibiting the generation of progeny by a subclass of pericytes led to decreased fibrosis and extracellular matrix deposition after spinal cord injury in mice. Regeneration of raphespinal and corticospinal tract axons was enhanced and sensorimotor function recovery improved following spinal cord injury in animals with attenuated pericyte-derived scarring. Using optogenetic stimulation, we demonstrate that regenerated corticospinal tract axons integrated into the local spinal cord circuitry below the lesion site. The number of regenerated axons correlated with improved sensorimotor function recovery. In conclusion, attenuation of pericyte-derived fibrosis represents a promising therapeutic approach to facilitate recovery following CNS injury. [Display omitted] •Inhibition of pericyte proliferation reduces fibrotic scar tissue following injury•Attenuated pericyte-derived scarring facilitates motor axon regeneration•Regenerated axons functionally re-integrate into the local spinal circuitry•Attenuated pericyte-derived scarring improves sensorimotor recovery Attenuation of fibrotic tissue generation by a subset of pericytes promotes regeneration of serotonergic and corticospinal tract axons and improves functional recovery after spinal cord injury.