TLR5 Activation through NF-κB Is a Neuroprotective Mechanism of Postconditioning after Cerebral Ischemia in Mice.
- Author:
Jaewon JEONG
1
;
Soojin KIM
;
Da Sol LIM
;
Seo Hea KIM
;
Heeju DOH
;
So Dam KIM
;
Yun Seon SONG
Author Information
- Publication Type:Original Article
- Keywords: Neuroprotection; Postconditioning; Cerebral ischemia; Toll-like receptor 5; Nuclear factor kappa B
- MeSH: 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
- From:Experimental Neurobiology 2017;26(4):213-226
- CountryRepublic of Korea
- Language:English
- 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.
