IKZF3 modulates cerebral ischemia/reperfusion injury by inhibiting neuroinflammation

Neuroinflammation is a key mediator to the pathogenic cascades induced by cerebral ischemia-reperfusion (I/R) injury. IKZF3, a key zinc finger transcription factor in the Ikaros family, has already been shown to modulate a wide range of cell functions and the production of inflammatory mediators. However, the effects of IKZF3 on inflammation and the potential mechanism after cerebral I/R injury remain unclear. In this study, we evaluated the effect of IKZF3 on HT-22 cells under oxygen-glucose deprivation and reoxygenation (OGD/R) in vitro and in mice with MACO in vivo. We found that IKZF3 expression peaked at 12 h after MCAO and OGD/R, and there was high expression of IKZF3 in brain tissues and HT-22 cells. IKZF3 knockdown exacerbated the damage by OGDinduced HT-22 cells injury and MCAO-induced brain injury in mice by regulating the production of inflammatory factors, which promoted the phosphorylation and nuclear transfer of NF-kappa B and may bind with NF-kappa B-p65 in vivo and in vitro. Our results suggested that IKZF3 may provide a new target in improve neurological recovery and reducing neuroinflammation after cerebral I/R injury.