Silencing CDKN2B-AS1 alleviates cognitive impairment caused by ischemic stroke by upregulating miR-140-3p levels

Objective Post-stroke cognitive impairment (PSCI) diagnosis primarily relies on scales, which are highly subjective. CDKN2B-AS1 is highly expressed in stroke patients. This study aims to investigate the clinical value and potential regulatory mechanisms of CDKN2B-AS1 in PSCI. Methods This study included 86 patients with PSCI. Cognitive function was assessed using the MoCA scales. A mouse PSCI model was established by treating mice with MCAO using the filament occlusion method. An in vitro PSCI model was constructed by treating HT22 cells with OGD/R. RT-qPCR was used to detect the expression of CDKN2B-AS1, miR-140-3p, Bax, Caspase-3, and Bcl-2 mRNA. ROC analysis evaluated the diagnostic value of CDKN2B-AS1. The Morris water maze assessed spatial learning and memory in mice. Cell proliferation, apoptosis, and inflammatory factors were measured using CCK-8 assay, flow cytometry, and ELISA, respectively. Results CDKN2B-AS1 is significantly upregulated in PSCI patients, with an AUC of 0.877 in ROC analysis. Its expression level is negatively correlated with MoCA scores. CDKN2B-AS1 has been demonstrated to directly bind and negatively regulate miR-140-3p. Knockdown of CDKN2B-AS1 alleviates OGD/R-induced neuronal apoptosis, inflammatory cytokine (IL-1β, IL-6, TNF-α) release, and oxidative stress levels by elevating miR-140-3p level. It also improves cognitive function in MCAO mice. These protective effects are reversed by miR-140-3p inhibition. Conclusion Silencing CDKN2B-AS1 may alleviate neuroinflammation and oxidative stress by upregulating miR-140-3p, thereby improving cognitive impairment. CDKN2B-AS1 holds potential as a diagnostic biomarker and therapeutic target for PSCI.