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

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 in HIBD. In our study performed on oxygen-glucose deprivation followed by reperfusion (OGD)/R-induced primary cortical neurons, a substantial reduction in was observed. Furthermore, the upregulation of significantly mitigated oxidative stress, apoptosis, and mitochondrial impairment. We demonstrated that 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, exhibited a negative correlation with . overexpression notably attenuated the protective effects of mimics, while knockdown of reversed the adverse effects of the inhibitor. Subsequently, we conducted an HIBD model in rats. experiments, 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 axis were confirmed in the HIBD model. may serve as a potential biomarker with significant therapeutic implications for HIBD.