Promoting astrocytic activity genetically and pharmacologically increases locomotor function after spinal cord injury in mice

After traumatic spinal cord injury (SCI), astrocytes become activated and through a cascade of events, lead to the formation of a glial scar. The glial scar has long been thought to be detrimental to recovery, via reduction of plasticity and axon growth, and the release of pro-inflammatory cytokines into the local environment. However, it has a beneficial role as well; astrocytes in the glial scar can provide a scaffold for growing axons, and the astroglial border functions to sequester the inflammatory lesion, prevent its detrimental expansion, and reduce secondary tissue loss. Therefore, promoting the glial border in the acute phases may promote functional recovery after SCI. We show that promoting astrogliosis by SOCS3 deletion, a negative regulator of STAT3, in primary astrocytes improves 'wound' closure in a wound healing assay. This was consistent in vivo with SOCS3 deletion in spinal astrocytes at the lesion site almost significantly reducing the size of the lesion and significantly improving functional locomotor recovery on a rotarod. Finding drugs that can promote acute wound healing (astroglial border formation) is of therapeutic interest. To this end, we developed an astrocytic wound healing assay that incorporates primary adult mouse astrocytes and a novel scratch tool that reduces variance and allows high-throughput capabilities. We identified Dyclonine, an FDA-approved sodium channel modulator, as a therapeutic candidate for SCI as it reduced the size of the wound in vitro and promoted locomotor function on a rotarod after SCI. We demonstrate here the utility of our astrocytic wound healing assay for the identification of new therapeutic strategies for SCI.