The neuroprotective effect of LncRNA MAGI2-AS3 against cerebral ischemia-reperfusion injury via targeting miR-218-5p

Objective: Long non-coding RNA (LncRNA) regulates neurological damage in cerebral ischemia-reperfusion (CIR) injury. The purpose of this study was to characterize the regulatory function of the LncRNA MAGI2 antisense RNA 3 (MAGI2-AS3) and explore its potential mechanism in CIR injury.

Methods: A rat middle cerebral artery occlusion/ischemia-reperfusion (MCAO/R) model was utilizedce, alongside an cell OGD/R model. Neurological deficits and infarct volume were assessed using the mNSS and TTC staining. The levels of MAGI2-AS3 and microRNA (miR)-218-5p were quantified using reverse transcription-quantitative polymerase chain reaction. Then, cell viability and apoptosis were determined via the Cell Count Kit-8 assay and flow cytometry. Oxidative stress indicators and the expression of neuroinflammatory factors were assessed via commercially available kits and an enzyme-linked immunosorbent assay. Finally, dual-luciferase reporter (DLR), RNA immunoprecipitation (RIP), and RNA pull-down assays confirmed the targeted interaction.

Results: MAGI2-AS3 was reduced in both MCAO/R and OGD/R models, accompanied by increased levels of lactate dehydrogenase (LDH), interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α, as well as decreased superoxide dismutase (SOD) levels. OGD/R reduced cell viability and promoted apoptosis. However, MAGI2-AS3 overexpression mitigated these effects by partially reversing the significant increases in mNSS score, cerebral infarct volume, and brain water content, while also suppressing oxidative stress and inflammation. Mechanistically, MAGI2-AS3 targets miR-218-5p and represses its expression. Furthermore, miR-218-5p significantly weakened the protective effects of MAGI2-AS3 overexpression in MACO/R and OGD/R models.

Conclusion: MAGI2-AS3 was initially identified as a potential protective agent against circulatory CIR. It exerts neuroprotective effects by targeting miR-218-5p, thereby alleviating neurological damage caused by such injury.