title: Selective antegrade cerebral perfusion attenuating the TLR4/NF-κB pathway during deep hypothermia circulatory arrest in a pig model.
abstract: OBJECTIVE
  The alteration of the Toll-like receptor/nuclear factor-kappa B (TLR4/NF-κB) signaling pathway during deep hypothermia circulatory arrest (DHCA) has not yet been defined. The aim of this study was to explore the expression of the TLR4/NF-κB pathway cytokine in cerebral injury resulting from DHCA as well as the effect of selective antegrade cerebral perfusion (SACP) on TLR4/NF-κB pathway expression.
  
  
  METHODS
  Twelve pigs were randomly assigned to DHCA alone (n = 6) or DHCA with SACP (n = 6) at 18°C for 80 min. Serum interleukin (IL)-6 was assayed by ELISA. Apoptosis and NF-κB proteins were detected by fluorescence TUNEL and Western blot, respectively. The level of TLR4 mRNA and protein were determined through qRT-PCR and Western blot.
  
  
  RESULTS
  The serum IL-6 level of the SACP group was significantly lower than that of the DHCA group at the end of circulation arrest and experimentation. Apoptotic index and NF-κB protein were apparently lower in SACP animals (p < 0.05). Compared to the DHCA group, the levels of TLR4 protein and mRNA in the SACP group were lower with significance (p < 0.05).
  
  
  CONCLUSIONS
  The TLR4/NF-κB signaling pathway plays a critical role in the pathogenesis of DHCA cerebral injury. Attenuation of the TLR4/NF-κB inflammatory cytokines probably contributes to the neuroprotective effect of SACP. The TLR4/NF-κB inflammatory signaling pathway may be a novel therapeutic target for developing a new strategy for neuroprotection in DHCA.
authors.affiliation: Second Department of Cardiac Surgery, Key Laboratory on Assisted Circulation of Health Ministry, Sun Yat-sen University, Guangzhou, China.
authors.forename: Zhi-Xian
authors.initials: ZX
authors.lastname: Tang
authors.forename: Guang-Xian
authors.initials: GX
authors.lastname: Chen
authors.forename: Meng-Ya
authors.initials: MY
authors.lastname: Liang
authors.forename: Jian
authors.initials: J
authors.lastname: Rong
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Yao
authors.forename: Xiao
authors.initials: X
authors.lastname: Yang
authors.forename: Zhong-Kai
authors.initials: ZK
authors.lastname: Wu
mesh_terms: D000818:Animals; D001921:Brain / Q000098:blood supply; D001930:Brain Injuries / Q000209:etiology* / Q000378:metabolism; D050792:Circulatory Arrest, Deep Hypothermia Induced / Q000009:adverse effects*; D003250:Constriction; D004195:Disease Models, Animal; D015850:Interleukin-6 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D011897:Random Allocation; D015424:Reperfusion; D015398:Signal Transduction; D013552:Swine; D013556:Swine, Miniature; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
chemical_list: D015850:Interleukin-6; D016328:NF-kappa B; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4