AC-YVAD-CMK Inhibits Caspase-1-mediated Imflammatory Response to Improve Bone Marrow Stromal Cells on Neuroprotection After Sci in Rats

Abstract Background: Stem cell transplantation maybe an advantaged method for curing spinal cord injury (SCI). However, the adverse environment of the injured area makes the treatment effects on transplantation unsatisfactory. The aim of this study was to investigate whether AC-YVAD-CMK could change enviroment by inhibiting caspase-1-mediated imflammatory response to improve Bone marrow stromal cells (BMSCs) transplantation on neuroprotection after SCI. Methods: Firstly, BMSCs were prepared and cultured in vitro and the SCI rat model was constructed. Then, AC-YVAD-CMK and BMSCs were injected into the SCI model at the same time. Western blot and ELISA were used to detect the production of inflammatory factors and neurotrophic factors in the injured area, meanwhile immunohistochemistry was employed to clarify the effect of AC-YVAD-CMK on BMSCs transplantation. Finally, we evaluated the recovery of limb motor function by BBB score in SCI rats. Result: In the AC-YVAD-CMK + BMSCs group, the active caspase-1, IL-18 and IL-1β expressed less than those in the BMSCs group or AC-YVAD-CMK group at 1 week after SCI ( P < 0.01). Meanwhile, increasing brain derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) levels, the PKH26 labeled BMSCs with some being neurofilament protein-200 (NF-200)-positive were still observed in the contusion site. Furthermore, the restoration of motor connections across the injury sites was positively correlated with the recovery of spinal cord function in cotreatment group ( P < 0.01). Conclusions: These results show that caspase-1-mediated inflammatory response is inhibited by AC-YVAD-CMK to enhance BMSCs transplantation to improve neuroprotection after SCI.