TLR5 Activation through NF-κB Is a Neuroprotective Mechanism of Postconditioning after Cerebral Ischemia in Mice
Experimental Neurobiology
;
: 213-226, 2017.
Article
in English
| WPRIM
| ID: wpr-22193
ABSTRACT
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.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Phosphorylation
/
In Vitro Techniques
/
Brain
/
Brain Ischemia
/
NF-kappa B
/
Neuroprotective Agents
/
Infarction, Middle Cerebral Artery
/
Immunoprecipitation
/
Toll-Like Receptor 5
/
Flagellin
Limits:
Animals
Language:
English
Journal:
Experimental Neurobiology
Year:
2017
Type:
Article
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