MicroRNA-124 negatively regulates STAT3 to alleviate hypoxic-ischemic brain damage by inhibiting oxidative stress.

MicroRNA-124 (miR-124) is implicated in various neurological diseases; however, its significance in hypoxic-ischaemic brain damage (HIBD) remains unclear. This study aimed to elucidate the underlying pathophysiological mechanisms of miR-124 in HIBD. In our study performed on oxygen-glucose deprivation followed by reperfusion (OGD)/R-induced primary cortical neurons, a substantial reduction in miR-124 was observed. Furthermore, the upregulation of miR-124 significantly mitigated oxidative stress, apoptosis, and mitochondrial impairment. We demonstrated that miR-124 interacts with the signal transducer and activator of transcription 3 (STAT3) to exert its biological function using the dual-luciferase reporter gene assay. As the duration of OGD increased, miR-124 exhibited a negative correlation with STAT3. STAT3 overexpression notably attenuated the protective effects of miR-124 mimics, while knockdown of STAT3 reversed the adverse effects of the miR-124 inhibitor. Subsequently, we conducted an HIBD model in rats. In vivo experiments, miR-124 overexpression attenuated cerebral infarction volume, cerebral edema, apoptosis, oxidative stress, and improved neurological function recovery in HIBD rats. In summary, the neuroprotective effects of the miR-124/STAT3 axis were confirmed in the HIBD model. MiR-124 may serve as a potential biomarker with significant therapeutic implications for HIBD.

MiR-155 promotes inflammation and apoptosis via targeting SIRT1 in hypoxic-ischemic brain damage.

Hypoxic-ischemic brain damage (HIBD) is one of the major causes of infant death and long-term neurological disturbances, which puts great pressure on families and society. Previous studies have reported that neuroinflammation regulates the pathogenesis of HIBD. MiR-155 has been reported to participate in many brain injuries; however, its direct implication and related mechanisms are not illuminated in HIBD. Herein, we identified that miR-155 plays a vital role in HIBD both in in vitro and in vivo models. We found that miR-155 promoted inflammation and apoptosis via targeting SIRT1 and negatively regulated its expression levels in oxygen-glucose deprivation/reoxygenation (OGD/R) in an in vitro model. Silencing of SIRT1 reversed the effects of miR-155 inhibitor on apoptosis and the NF-κB pathway in OGD/R-treated PC12 cells and microglia (BV2) cells. Moreover, in a neonatal rat HIBD model, miR-155 enhanced apoptosis and inflammation in the brains of rats with HIBD in vivo. Together, our results demonstrated that miR-155 exerted a negative effect in HIBD by targeting SIRT1, which could contribute to the treatment of neonatal patients with hypoxic-ischemic brain damage.