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

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.

Wang L ，Lu Y ，Guan H ，Jiang D ，Guan Y ，Zhang X ，Nakano H ，Zhou Y ，Zhang Y ，Yang L ，Li H ... -  《-》

Mindin is a critical mediator of ischemic brain injury in an experimental stroke model.

Stroke is the second leading cause of death among adults worldwide. Mindin is an ECM protein that plays important roles in regulating inflammation, angiogenesis and neuronal outgrowth. The role of mindin in the context of brain ischemia has not been examined. Transient occlusion of the middle cerebral artery was performed on mindin knockout (KO) mice, mice that carried a neuron-specific constitutively active mindin transgene (TG) and the appropriate controls. The outcome of the ischemia was evaluated by examination of the infarct and edema volumes and by neurological score assessments. The brains were collected 24 h or 3 days following the induced stroke. Compared with the control mice, the mindin KO mice exhibited lower infarct volumes and better outcomes in the neurological tests. Mindin-deficient mice exhibited low expression levels of stroke-induced inflammatory mediators, an attenuated recruitment of inflammatory cells, and inhibited activation of NF-κB. The neuronal apoptosis levels were also lower in the brains of the mindin KO mice than in those of the control mice. The mice that expressed a neuron-specific, constitutively active mindin transgene exhibited effects following the cerebral ischemic injury that were the opposite of those that were observed in the mindin KO mice. Moreover, Akt signaling activation was elevated in the ischemic brains of mindin KO mice. Mindin KO mice exhibited minor infarctions, an attenuated inflammatory response and low levels of neuronal apoptosis following an ischemic insult. These data demonstrate that mindin is a critical mediator of ischemic brain injury in an experimental stroke model. Akt signaling most likely mediates the biological function of mindin in this model of cerebral ischemia.

Wang L ，Lu Y ，Zhang X ，Zhang Y ，Jiang D ，Dong X ，Deng S ，Yang L ，Guan Y ，Zhu L ，Zhou Y ，Zhang X ，Li H ... -  《-》

Disruption of Tumor Necrosis Factor Receptor-Associated Factor 5 Exacerbates Murine Experimental Colitis via Regulating T Helper Cell-Mediated Inflammation.

Shang J ，Li L ，Wang X ，Pan H ，Liu S ，He R ，Li J ，Zhao Q ... -  《-》

Increased inflammation and brain injury after transient focal cerebral ischemia in activating transcription factor 3 knockout mice.

Activating transcription factor 3 (ATF3) is a stress-induced transcription factor that has been shown to repress inflammatory gene expression in multiple cell types and diseases. This study was conducted to investigate the role of ATF3 in the pathological processes of cerebral ischemia and its influence on post-ischemic inflammation. Wild-type (WT) and ATF3 knockout (KO) mice were subjected to middle cerebral artery occlusion (45 min) followed by reperfusion. Infarct volume, brain edema, and neurological deficits were examined. Neural apoptosis, inflammatory gene expression, cellular inflammatory response and Matrix Metallo Proteinases 9 (MMP9) activity were assessed. Activity of the nuclear factor-kappa B (NF-κB) signaling pathway and cAMP-responsive element-binding protein (CREB) was studied. Knockout of ATF3 significantly exacerbated the infarct volume and worsened neurological function after brain ischemia. Neural apoptosis, inflammatory gene expression and cellular inflammatory response were upregulated in ATF3 KO mice. The MMP9 mRNA expression and protein activity were increased in ATF3 KO mice. KO of ATF3 led to an elevation in the activity of the NF-κB signaling pathway and inhibition of CREB activity. Our study demonstrated that ATF3 was markedly induced by brain ischemia. ATF3 deficiency exacerbated the inflammatory response and brain injury after cerebral ischemia, potentially through further activation of the NF-κB signaling pathway. ATF3 is likely an important protective regulator in cerebral ischemic injury.

Wang L ，Deng S ，Lu Y ，Zhang Y ，Yang L ，Guan Y ，Jiang H ，Li H ... -  《-》

Adenosine A 2A receptor deficiency reduces striatal glutamate outflow and attenuates brain injury induced by transient focal cerebral ischemia in mice.

Gui L ，Duan W ，Tian H ，Li C ，Zhu J ，Chen JF ，Zheng J ... -  《-》