Selective inhibition of STAT1 reduces spinal cord injury in mice.

The signal transducer and activator of transcription 1 (STAT1) is associated with neuronal cell death after cerebral ischemia. However, the role of STAT1 in the spinal cord injury (SCI) remains unclear. Here, we examined whether STAT1 blockade reduces neural tissue damage and locomotor impairment after SCI in mice. The small interfering RNA against STAT1 (STAT1 siRNA) or control non-targeting siRNA was injected intraperitoneally into SCI mice. Histological damage and locomotor function were evaluated. Inflammatory markers and apoptosis were determined. STAT1 siRNA treatment significantly decreased the histological damage following SCI. STAT1 siRNA-treated mice showed significantly improved locomotor function compared with the controls. Furthermore, TNF-α, IL-1β, and IL-6 levels at the injured site from the STAT1 siRNA-treated group were significantly reduced and IL-10 increased, in comparison with controls. The NF-κB activation and apoptosis in SCI were also inhibited. These results reveal that selective STAT1 inhibition reduced neural tissue damage and locomotor impairment by regulating inflammatory response and possibly apoptosis. STAT1 represents a novel therapeutic target after SCI.