Lang Wang and Yanyun Lu contributed equally to this work.
Tumor necrosis factor receptor-associated factor 5 is an essential mediator of ischemic brain infarction
Article first published online: 18 MAR 2013
© 2013 International Society for Neurochemistry
Journal of Neurochemistry
Volume 126, Issue 3, pages 400–414, August 2013
How to Cite
J. Neurochem. (2013) 126 400–414.
- Issue published online: 18 JUL 2013
- Article first published online: 18 MAR 2013
- Accepted manuscript online: 16 FEB 2013 01:21PM EST
- Manuscript Accepted: 14 FEB 2013
- Manuscript Revised: 20 JAN 2013
- Manuscript Received: 20 OCT 2012
- National Natural Science Foundation of China. Grant Numbers: 81100230, 81070089
- National Science and Technology Support Project. Grant Numbers: 2011BAI15B02, 2012BAI39B05
- National Basic Research Program of China. Grant Number: 2011CB503902
- Special Funds for Basic Research and Operating Expenses of the Central Universities. Grant Number: 4101032
- blood-brain barrier;
Tumor necrosis factor receptor-associated factor 5 (TRAF5) 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 TRAF5 in the context of brain ischemia/reperfusion (I/R) injury. Transient occlusion of the middle cerebral artery was performed on TRAF5 knockout mice (KO), neuron-specific TRAF5 transgene (TG), and the appropriate controls. Compared with the WT mice, the TRAF5 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 TRAF5 KO mice. TRAF5 TG mice exhibited an opposite phenotype. Moreover, the Akt/FoxO1 signaling pathway was enhanced in the ischemic brains of the TRAF5 KO mice. These results provide the first demonstration that TRAF5 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 TRAF5 in this model.