Sox9 knock‐down in mice improves locomotor recovery after spinal cord injury by reducing CSPG levels and facilitating reactive sprouting

Abstract

We have identified the transcription factor SOX9 as a key regulator of chondroitin sulfate proteoglycan (CSPG) production in the injured spinal cord. CSPGs in the lesion epicenter are produced by reactive astrocytes responding to the injury. CSPGs are also key components of the perineuronal matrix that surround the cell bodies and dendrites of many neurons in the central nervous system. Thus CSPGs may limit plasticity after SCI by inhibiting regeneration of axons through the glial scar or by inhibiting reactive sprouting at deafferented targets distant to the lesion. We have demonstrated reduced CSPG levels and improved locomotor recovery in spinal cord‐injured Sox9 conditional knockout mice. Herein we investigated sparing, long‐range regeneration and reactive sprouting as possible explanations for the improved locomotor outcomes in Sox9 knockout mice after SCI. We herein demonstrate that the improved recovery of locomotor function in Sox9 conditional knockout mice after SCI is due to increased reactive sprouting secondary to reduced CSPG levels distal to the lesion.