Exp Neurobiol.  2017 Aug;26(4):213-226. 10.5607/en.2017.26.4.213.

TLR5 Activation through NF-κB Is a Neuroprotective Mechanism of Postconditioning after Cerebral Ischemia in Mice

• Jeong J
• Kim S
• Lim DS
• Kim SH
• Doh H
• Kim SD
• Song YS

• KMID: 2389008
• DOI: http://doi.org/10.5607/en.2017.26.4.213

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.

Keyword

Neuroprotection; Postconditioning; Cerebral ischemia; Toll-like receptor 5; Nuclear factor kappa B

MeSH Terms

Animals
Brain
Brain Ischemia*
Flagellin
Immunoprecipitation
In Vitro Techniques
Infarction, Middle Cerebral Artery
Mice*
Neuroprotection
Neuroprotective Agents
NF-kappa B
Phosphorylation
Toll-Like Receptor 5
Flagellin
NF-kappa B
Neuroprotective Agents
Toll-Like Receptor 5