Abstract
Spinal cord injury (SCI) is a serious condition that affects bodily function; however, there is no effective therapy in clinical practice. MCC950, a selective NOD-like receptor protein-3 (NLRP3) inflammasome inhibitor, has been reported to alleviate canonical and non-canonical NLRP3 inflammasome activation of the inflammatory response in vitro and in vivo. However, the effect of MCC950 treatment on neurological post-SCI recovery remains unclear. In this study, we assessed the pharmacological effect of MCC950 on an experimental SCI model in vivo and neuronal injury in vitro. We found that MCC950 improved the grip strength, hind limb movements, spinal cord edema, and pathological injury in the SCI mice. We demonstrated that it exerted this effect by blocking NLRP3 inflammasome assembly, including NLRP3-ASC and NLRP3-Caspase-1 complexes, as well as the release of pro-inflammatory cytokines TNF-α, IL-1β, and IL-18. Moreover, we found that MCC950 reduced spinal neuron injury and NLRP3 inflammasome activation, which had been induced by oxygen–glucose deprivation (OGD) or lipopolysaccharides (LPS) in vitro. In conclusion, our findings indicate that MCC950 alleviates inflammatory response and improves functional recovery in the acute mice model of SCI by blocking NLRP3 inflammasome assembly and alleviating downstream neuroinflammation. Therefore, these findings could prove useful in the development of effective therapeutic strategies for the treatment and prognosis of SCI.
Highlights
Spinal cord injury (SCI) is a serious condition that affects bodily function
These results indicate that MCC950 treatment ameliorates motor function impairment in SCI mice
We examined whether MCC950 treatment altered the NOD-like receptor protein-3 (NLRP3) inflammasome activation pathway in spinal neurons after oxygen–glucose deprivation (OGD) or LPS exposure
Summary
Spinal cord injury (SCI) is a serious condition that affects bodily function. There is post-SCI activation of NLRP3 inflammasome in an animal model involving microglia and spinal cord tissue (Grace et al, 2016; Jiang et al, 2016; Zendedel et al, 2016). Previous studies have reported means of reducing neuroinflammation and promoting functional recovery in SCI animals by suppressing NLRP3 inflammasome activity (Qian et al, 2017; Zhu et al, 2017). Jiang et al (2017) reported that suppression of NLRP3 inflammasome activity to control neuroinflammation using the small-molecule inhibitor BAY 11-7082 or A438079 could attenuate mitochondria damage, alleviate SCI, and improve neuronal function restoration in a mouse model of SCI Previous studies have reported means of reducing neuroinflammation and promoting functional recovery in SCI animals by suppressing NLRP3 inflammasome activity (Qian et al, 2017; Zhu et al, 2017). Jiang et al (2017) reported that suppression of NLRP3 inflammasome activity to control neuroinflammation using the small-molecule inhibitor BAY 11-7082 or A438079 could attenuate mitochondria damage, alleviate SCI, and improve neuronal function restoration in a mouse model of SCI
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
