MCC950 attenuated early brain injury by suppressing NLRP3 inflammasome after experimental SAH in rats

Abstract

Nucleotide oligomerization domain(NOD)-like receptor protein-3(NLRP3) inflammasome is a multiprotein complex, which results in the inflammatory response in early brain injury(EBI) after subarachnoid hemorrhage(SAH). MCC950, a specific NLRP3 inhibitor, plays neuroprotective effects in several central nervous system diseases. However, the role of MCC950 in SAH remains elusive. This study aims to investigate whether MCC950 exerts neuroprotection after experimental SAH and further explore the potential mechanisms. The SAH model was induced by endovascular perforation process using adult male Sprague-Dawley rats. MCC950 was injected intraperitoneally 1 h after SAH with a dose of 10 mg/kg. The results showed that MCC950 significantly ameliorated severe brain edema and neurological dysfunction. Furthermore, MCC950 efficiently reduced NLRP3 inflammasome expression as well as the pro-inflammatory cytokines, such as TNF-α, IL-1ß, and IL-6. In addition, the protective effect of MCC950 was blunted by lipopolysaccharide. In conclusion, our findings suggest that MCC950 alleviated SAH-induced EBI by suppressing inflammation.