Long Non-Coding RNA 1810026B05Rik Mediates Cerebral Ischemia/Reperfusion-Induced Neuronal Injury Through NF-κB Pathway Activation.

Abstract

Cerebral ischemia/reperfusion (I/R) injury remains a significant contributor to adult neurological morbidity, primarily due to exacerbated neuroinflammation and cell apoptosis. These processes amplify brain damage through the release of various pro-inflammatory cytokines and pro-apoptotic mediators. Although long non-coding RNAs (lncRNAs) are increasingly recognized for their involvement in regulating diverse biological pathways, their precise role in cerebral I/R injury has not been fully elucidated. In the current study, transcriptomic profiling was conducted using a rat model of focal cerebral I/R, leading to the identification of lncRNA-1810026B05Rik-also referred to as CHASERR-as a novel lncRNA responsive to ischemic conditions. The elevated expression of this lncRNA was observed in mouse brain tissues subjected to middle cerebral artery occlusion followed by reperfusion (MCAO/R), as well as in primary cortical neurons derived from rats exposed to oxygen-glucose deprivation and subsequent reoxygenation (OGD/R). The results suggested that lncRNA-1810026B05RiK mediates the activation of the nuclear factor-kappaB (NF-κB) signaling pathway by physically binding to NF-kappa-B inhibitor alpha (IκBα) and promoting its phosphorylation, thus leading to neuroinflammation and neuronal apoptosis during cerebral ischemia/reperfusion. In addition, lncRNA-1810026B05Rik knockdown acts as an NF-κB inhibitor in the OGD/R and MCAO/R pathological processes, suggesting that lncRNA-1810026B05Rik downregulation exerts a protective effect on cerebral I/R injury. In summary, the lncRNA-1810026B05Rik has been identified as a critical regulator of neuronal apoptosis and inflammation through the activation of the NF-κB signaling cascade. This discovery uncovers a previously unrecognized role of 1810026B05Rik in the molecular mechanisms underlying ischemic stroke, offering valuable insights into disease pathology. Moreover, its involvement highlights its potential as a novel therapeutic target, paving the way for innovative treatment strategies for stroke patients.