ABSTRACT NUMBER: ESOC2026A903 MAF1 LOSS ATTENUATED ACUTE ISCHEMIC STROKE INJURY BY INHIBITING NLRP3-MEDIATED PYROPTOSIS

Abstract Background and aims Acute ischemic stroke (AIS) is the second leading cause of death worldwide with high disability and mortality rates. Recent studies indicated vital role of transcriptional regulator MAF1 in neurological diseases.This study aims to reveal the key role and mechanisms of transcriptional regulator MAF1 in AIS. Methods Behavioral assessment of sensorimotor function was evaluated in transient middle cerebral artery occlusion (tMCAO) model mice. MAF1 expression change was detected through Polymerase Chain Reaction, Western blot and Immunofluorescence staining. Also, in vitro verification was performed in oxygen glucose deprivation/reperfusion (OGD/R) model. Stereotactic injection of AAV-hsyn-shMAF1 was used for assessing MAF1 knockdown effect on neurological function of tMCAO mice. RNA sequencing was performed to identify differentially expressed genes between OGD/R-Lenti-shMAF1 and OGD/R-Lenti-SCR groups. Western blot analysis was further applied to examine downstream molecular alterations. Results MAF1 expression was significantly increased in animal and cellular models of AIS. Conditional MAF1 knockdown alleviated neurological deficits after tMCAO modelling. RNA sequencing revealed altered expression of NLRP3-related pyroptosis proteins and pathways following MAF1 knockdown in OGD/R-treated primary neurons. Downregulation of MAF1 led to inhibited expression of NLRP3 pathways in both tMCAO mouse and OGD/R cell models. Conclusions MAF1 was upregulated in the peri-infarct cortex of AIS model.MAF1 Knockdown attenuated ischemic cerebral injury by regulating NLRP3-mediated pyroptosis. These findings identify MAF1 as a potential diagnostic biomarker and a unique therapeutic target for improving functional recovery in AIS patients. Conflict of interest Xue Gao. nothing to disclose