Targeting IKK/NF-κB pathway reduces infiltration of inflammatory cells and apoptosis after spinal cord injury in rats

Abstract

IKK/NF-κB pathway is a principal player in the regulation of inflammation and apoptosis in spinal cord injury (SCI). We have previously shown that BMS-345541, a selective inhibitor of IKK, could inhibit NF-κB activation and ameliorate the motor function of hind limbs in rats after SCI. However its neuroprotective mechanism in SCI is still unclear. In this study, we investigated the neuroprotective effects of BMS-345541 and possible mechanisms by which BMS-345541 acts against inflammatory cells infiltration and apoptosis in rat SCI models. SCI induced neutrophils infiltration when examined by myeloperoxidase activity, which was prevented by BMS-345541 through inhibiting the expression of ICAM-1. BMS-345541 inhibited activation of caspase-3, and attenuated apoptotic cell death in spinal cord by modulating Bcl-2 and Bax expression following SCI. Our study indicates that BMS-345541 may play an important role on the anti-inflammatory and anti-apoptotic effects with experimental SCI. Our results imply the IKK inhibitors may be useful in the therapy of spinal cord injury.