miR-8485 by Targeting ITGAM Expression Alleviates Cognitive Impairment Induced by Ischemic Stroke

ObjectivePost-stroke cognitive impairment (PSCI) is a major complication of ischemic stroke (IS). This study aims to explore the role of miR-8485 in PSCI and its underlying molecular mechanism.Methods84 PSCI patients and 90 post-stroke cognitively normal (PSCN) patients were included. Serum miR-8485 and ITGAM expression were examined via reverse transcription quantitative polymerase chain reaction. The diagnostic efficacy of miR-8485 was evaluated by receiver operating characteristic (ROC) curve. Risk factors of PSCI were determined via logistic regression analysis. An in vitro PSCI cell model was constructed through oxygen-glucose deprivation/reoxygenation (OGD/R). Cell viability, apoptosis and inflammatory factor levels were determined by Cell Counting Kit-8 assay, flow cytometry and enzyme-linked immunosorbent assay. The oxidative stress was evaluated by measuring superoxide dismutase (SOD), malondialdehyde (MDA) and catalase (CAT) levels. The interaction between miR-8485 and ITGAM was verified by dual-luciferase reporter assay.ResultsmiR-8485 was downregulated in PSCI patients, and ROC analysis showed that it could differentiate PSCI patients from PSCN patients. Downregulated miR-8485 expression was associated with PSCI disease severity. In OGD/R-treated human microglial cells (HMC3), upregulation of miR-8485 increased cell viability, suppressed inflammatory responses and oxidative stress, and inhibited apoptosis. ITGAM was the target of miR-8485. Overexpression of ITGAM partially reversed the protective effect of miR-8485 upregulation in OGD/R-induced HMC3 cells.ConclusionmiR-8485 alleviates OGD/R-induced inflammatoty responses and oxidative stress via targeted inhibition of ITGAM expression. The miR-8485/ITGAM axis may serve as a key regulatory pathway and a potential therapeutic candidate for further investigation in PSCI.