Remimazolam alleviates cerebral ischemia–reperfusion injury of rats by inhibiting NF-κB/NLRP3 inflammasome pyroptosis

Abstract

Neuroinflammation is closely associated with activation of NLRP3 inflammasome after acute ischemic stroke. Our previous study preliminarily found that remimazolam mitigated cerebral ischemia-reperfusion (I/R) injury in MCAO rats, possibly by inhibiting the expression of the NLRP3 inflammasome pathway. Previous studies showed that the prime and activation of NLRP3 inflammasome are regulated by NF-κB. Therefore, the exact mechanism of the effect of remimazolam on I/R injury needs further study. Rat MCAO I/R injury model and primary cultured rat cortical neurons OGD/R injury model were used to investigate the effect of remimazolam on reducing neuronal pyroptosis. The neurological deficit score assessed neurological function. Cerebral infarct volume was measured using TTC staining. Cell viability and injury were assessed by CCK-8 and LDH. Cell pyroptosis was evaluated using TEM. The mRNA levels of the NF-κB/NLRP3 inflammasome signaling pathway were assessed using qPCR. Western blotting and immunofluorescence staining detected the protein expression of the NF-κB/NLRP3 inflammasome signaling pathway. Remimazolam alleviates cerebral infarct volume and neurological deficit in MCAO rats, increases cell viability, and decreases LDH release of OGD/R cortical neurons. TEM showed that after remimazolam treatment, a significant reduction in the pyroptosis of neurons both in vivo and in vitro. Furthermore, remimazolam down-regulated the mRNA levels and protein expression of NF-κB, NLRP3, ASC, and Caspase-1, and reduced the release of IL-1β. Remimazolam may attenuate cortical neuronal pyroptosis by inhibiting NF-κB mediated activation of NLRP3 inflammasome after acute I/R injury.

Keywords

Affiliated Institutions

• Sichuan Cancer Hospital CN
• University of Electronic Science and Technology of China CN
• First Affiliated Hospital of GuangXi Medical University CN
• Guangxi Medical University CN
• Guilin Medical University CN

Related Publications