Tumor necrosis factor receptor‐associated factor 5 is an essential mediator of ischemic brain infarction

Tumor necrosis factor receptor‐associated factor 5 ( TRAF 5) is an adaptor protein of the tumor necrosis factor ( TNF ) receptor superfamily and the interleukin‐1 receptor/Toll‐like receptor superfamily and plays important roles in regulating multiple signaling pathways. This study was conducted to investigate the role of TRAF 5 in the context of brain ischemia/reperfusion (I/R) injury. Transient occlusion of the middle cerebral artery was performed on TRAF 5 knockout mice ( KO ), neuron‐specific TRAF 5 transgene ( TG ), and the appropriate controls. Compared with the WT mice, the TRAF 5 KO mice showed lower infarct volumes and better outcomes in the neurological tests. A low neuronal apoptosis level, an attenuated blood‐brain barrier ( BBB ) disruption and an inhibited inflammatory response were exhibited in TRAF 5 KO mice. TRAF 5 TG mice exhibited an opposite phenotype. Moreover, the Akt/FoxO1 signaling pathway was enhanced in the ischemic brains of the TRAF 5 KO mice. These results provide the first demonstration that TRAF 5 is a critical mediator of I/R injury in an experimental stroke model. The Akt /FoxO1 signaling pathway probably plays an important role in the biological function of TRAF 5 in this model.