Beneficial effects of chlorogenic acid treatment on neuroinflammation after deep hypothermic circulatory arrest may be mediated through CYLD/NF-κB signaling.

Deep hypothermic circulatory arrest (DHCA) during heart surgery may induce neuroinflammation leading to neurocognitive dysfunction. Chlorogenic acid (CA) is a common phytochemical, which can attenuate neuroinflammation. Nevertheless, the underlying mechanism involved in the anti-inflammatory effect of CA after DHCA is unknown. The present study therefore characterized the anti-inflammatory functions of CA after DHCA using in vivo and in vitro DHCA models. The activation of microglia, inflammatory cytokine levels, and the NF-κB pathway were measured. The results showed that CA treatment ameliorated neurocognitive function and reduced the inflammatory cytokine levels in the brain and circulation. Furthermore, the microglial and NF-κB activations were suppressed after DHCA. CA exerted the same anti-inflammatory effect in hypothermia OGD microglial cells as the in vivo study. Additional studies indicated that the regulation of ubiquitin ligase activity of TRAF6 and RIP1 by CYLD was related to the mechanism involving inhibition of CA in the NF-κB pathway. Together, the results showed that CA may attenuate neuroinflammation after DHCA by modulating the signaling of CYLD/NF-κB.