title: Improved Survival and Neurological Outcomes after Cardiopulmonary Resuscitation in Toll-like Receptor 4-mutant Mice.
abstract: BACKGROUND
  Toll-like receptor 4 (TLR4) is a crucial receptor in the innate immune system and noninfectious immune responses. It has been reported that TLR4 participates in the pathological course of ischemia/reperfusion (I/R) injury. However, the role of TLR4 in the process of I/R injury after cardiac arrest (CA) and cardiopulmonary resuscitation (CPR) is still unknown. In this study, we investigated the effects of TLR4 mutation on survival and neurological outcome in a mouse model of CA/CPR.
  
  
  METHODS
  A model of potassium-induced CA was performed on TLR4-mutant mice (C3H/HeJ) and wild-type mice (C3H/HeN). After 3 min of untreated CA, resuscitation was attempted with chest compression, ventilation, and intravenous epinephrine. Behavioral tests were performed on mice on day 3 after CPR. The morphological changes in hippocampal neurons were assessed by light and electron microscopy. Expressions of TLR4 and intercellular adhesion molecule-1 (ICAM-1) were detected by Western blot. Levels of tumor necrosis factor-α (TNF-α) and myeloperoxidase (MPO) were measured with enzyme-linked immunosorbent assay (ELISA).
  
  
  RESULTS
  On day 3 after resuscitation the overall mortality was 33.33% in C3H/HeJ group compared with 53.33% in C3H/HeN group (P < 0.05). And there was much higher central tendency in C3H/HeJ group than C3H/HeN group during open field test (P < 0.05). Meanwhile, the percentage of nonviable neurons was 21.16% in C3H/HeJ group compared with 53.11% in C3H/HeN group (P < 0.05). And there were significantly lower levels of hippocampal TNF-α and MPO in C3H/HeJ mice (TNF-α: 6.85±1.19 ng/mL, MPO: 0.33±0.11 U/g) than C3H/HeN mice (TNF-α: 11.36±2.12 ng/mL, MPO: 0.54±0.17 U/g) (all P < 0.01). CPR also significantly increased the expressions of TLR4 and ICAM-1 in C3H/HeN group. However, the expression of ICAM-1 was much lower in C3H/HeJ group than in C3H/HeN group after CPR (P < 0.01).
  
  
  CONCLUSIONS
  TLR4 signaling is involved in brain damage and in inflammation triggered by CA/CPR.
authors.forename: Li
authors.initials: L
authors.lastname: Xu
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhang
authors.forename: Qing-Song
authors.initials: QS
authors.lastname: Zhang
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.forename: Ji-Yuan
authors.initials: JY
authors.lastname: Han
authors.affiliation: Department of Emergency, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Sun
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000276:immunology / Q000378:metabolism; D016887:Cardiopulmonary Resuscitation / Q000379:methods*; D006323:Heart Arrest / Q000235:genetics / Q000378:metabolism* / Q000628:therapy*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008297:Male; D051379:Mice; D009154:Mutation; D009195:Peroxidase / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000235:genetics* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D009195:Peroxidase