Conditional Sox9 ablation 30 days after spinal cord injury: Testing the therapeutic value of a successful acute strategy to increase neuroplasticity in a model of chronic spinal cord injury
Many individuals who have suffered from spinal cord injury (SCI) have longstanding damage. The molecular environment of the spinal cord is not permissive to axonal growth and neuroplasticity after injury is limited. Perineuronal nets containing chondroitin sulfate proteoglycans (CSPGs) are major inhibitors of axonal sprouting. Our laboratory has identified that the transcription factor SOX9 regulates a battery of genes involved in CSPG biosynthesis. Using Sox9 conditional knockout mice, we have shown that ablating Sox9 before injury decreases CSPG levels in the cord, increases reparative sprouting, and leads to improved locomotor recovery. However, it is unknown whether Sox9 ablation following SCI leads to similar recovery. To investigate this, Sox9 was ablated in mice 30 days after SCI. This ablation did not decrease levels of perineuronal nets, increase neuroplasticity or improve locomotor recovery compared to controls. These results will be discussed in the context of CSPG turnover rate and matrix metalloproteinase activity
