Edaravone Modulates NLRP3 Inflammasome Component Expression and Attenuates Glial Cell Morphological Alterations After Status epilepticus
摘要
After a status epilepticus (SE) event, the NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) inflammasome is activated, accompanied by morphological alterations in microglia and astrocytes, which are key features of inflammation. Antioxidants have been shown to inhibit NLRP3 inflammasome activation and suppress glial cell morphological alterations. In this study, firstly we evaluated the antiseizure effect of the antioxidant edaravone (EDA) at different doses on the convulsive behavior and epileptiform activity induced by pilocarpine (Pilo) in order to determine the most appropriate dose for subsequent experiments. Later, for the main study, we investigated the temporal expression of NLRP3 inflammasome components and glial cell morphological characteristics following SE to assess the efficacy of the EDA, using a rat model of SE induced by Pilo and conducted a temporal analysis of the protein expression of NLRP3, IL-1β, caspase-1 p20 and IL-10 by nano dot blotting. Additionally, Sholl analysis was performed to evaluate glial cell morphology. Our findings revealed an increase in the expression of NLRP3 inflammasome components after SE, accompanied by glial cell morphological changes characteristic of a reactive state. Furthermore, EDA significantly reduced NLRP3 expression, decreased IL-10 levels and mitigated SE-induced morphological alterations in glial cells.