TLR5 Activation through NF-κB Is a Neuroprotective Mechanism of Postconditioning after Cerebral Ischemia in Mice
نویسندگان
چکیده
Postconditioning has been shown to protect the mouse brain from ischemic injury. However, the neuroprotective mechanisms of postconditioning remain elusive. We have found that toll-like receptor 5 (TLR5) plays an integral role in postconditioning-induced neuroprotection through Akt/nuclear factor kappa B (NF-κB) activation in cerebral ischemia. Compared to animals that received 30 min of transient middle cerebral artery occlusion (tMCAO) group, animals that also underwent postconditioning showed a significant reduction of up to 60.51% in infarct volume. Postconditioning increased phospho-Akt (p-Akt) levels and NF-κB translocation to the nucleus as early as 1 h after tMCAO and oxygen-glucose deprivation. Furthermore, inhibition of Akt by Akt inhibitor IV decreased NF-κB promoter activity after postconditioning. Immunoprecipitation showed that interactions between TLR5, MyD88, and p-Akt were increased from postconditioning both in vivo and in vitro. Similar to postconditioning, flagellin, an agonist of TLR5, increased NF-κB nuclear translocation and Akt phosphorylation. Our results suggest that postconditioning has neuroprotective effects by activating NF-κB and Akt survival pathways via TLR5 after cerebral ischemia. Additionally, the TLR5 agonist flagellin can simulate the neuroprotective mechanism of postconditioning in cerebral ischemia.
منابع مشابه
Attenuating of NF-Κb/VCAM-1 Expression in Middle Cerebral Artery Occlusion (MCAO) Model by Viola Odorata: Protection Against Injury Ischemia- Reperfusion Injury in Rats
Background: The death of neurons and cerebral edema are the main consequences of stroke. However, inflammatory processes play a key role in aggravating cerebral damage following stroke. The aim of this study was to investigate the effects of Viola odorant extract (VOE) on infarct volume (IV), neurologic deficits (ND), and expression of NF-κB and VCAM-1 in the MCAO model. Method: The animals we...
متن کاملProtection of Ischemic Postconditioning against Neuronal Apoptosis Induced by Transient Focal Ischemia Is Associated with Attenuation of NF-κB/p65 Activation
BACKGROUND AND PURPOSE Accumulating evidences have demonstrated that nuclear factor κB/p65 plays a protective role in the protection of ischemic preconditioning and detrimental role in lethal ischemia-induced programmed cell death including apoptosis and autophagic death. However, its role in the protection of ischemic postconditioning is still unclear. METHODS Rat MCAO model was used to prod...
متن کاملThe effects of adenosine injection after of brain ischemia reperfusion injury on gene expression of NF-kB/p65 and activity level of ROS in male Wistar rats
Background: Unit of p65 is one of the subunits of NF-κB and its phosphorylation by stress oxidative causes activation of NF-κB. The aim of present study was to investigate the effects of adenosine injection after brain ischemia reperfusion injury on gene expression of NF-κB /p65 and Reactive Oxygen Species (ROS) in hippocampus tissue of male wistar rats. Methods: 40 male wistar rats were rando...
متن کاملNeuroprotective Consequences of Postconditioning on Embolic Model of Cerebral Ischemia in Rat
متن کامل
Sevoflurane Postconditioning-Induced Anti-Inflammation via Inhibition of the Toll-Like Receptor-4/Nuclear Factor Kappa B Pathway Contributes to Neuroprotection against Transient Global Cerebral Ischemia in Rats
The anti-inflammatory actions of sevoflurane postconditioning are suggested as an important mechanism of sevoflurane postconditioning-induced neuroprotection against cerebral ischemia. Here, we determined whether the anti-inflammatory effects of sevoflurane postconditioning were mediated via inhibition of the toll-like receptor (TLR)-4/nuclear factor kappa B (NF-κB) pathway after global transie...
متن کامل