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KMID : 0892920170260040213
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Experimental Neurobiology
2017 Volume.26 No. 4 p.213 ~ p.226
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TLR5 Activation through NF-κB Is a Neuroprotective Mechanism of Postconditioning after Cerebral Ischemia in Mice
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Jeong Jae-Won
Kim Soo-Jin
Lim Da-Sol
Kim Seo-Hea
Doh Hee-Ju
Kim So-Dam
Song Yun-Seon
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Abstract
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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.
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KEYWORD
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Neuroprotection, Postconditioning, Cerebral ischemia, Toll-like receptor 5, Nuclear factor kappa B
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