Improved Survival and Neurological Outcomes after Cardiopulmonary Resuscitation in Toll-like Receptor 4-mutant Mice

• Published in: Chinese medical journal Vol. 128; no. 19; pp. 2646 - 2651
• Main Authors: Xu, Li, Zhang, Qing, Zhang, Qing-Song, Li, Qian, Han, Ji-Yuan, Sun, Peng
• Format: Journal Article
• Language: English
• Published: China Medknow Publications Pvt Ltd 05.10.2015; Medknow Publications and Media Pvt. Ltd; Lippincott Williams & Wilkins Ovid Technologies; Department of Emergency,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,Hubei 430022,China%Department of Anesthesia,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,Hubei 430022,China%Department of Urology,Liyuan Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,Hubei 430022,China%Department of Emergency,Wuhan First Hospital,Wuhan,Hubei 430022,China; Medknow Publications & Media Pvt Ltd; Wolters Kluwer
• Subjects: Animals; Anxiety; Blotting, Western; Brain - immunology; Brain - metabolism; Cardiac arrest; Cardiac Arrest; Cardiopulmonary Resuscitation; Cerebral Injury; Toll-like Receptor 4; Cardiopulmonary resuscitation; Cardiopulmonary Resuscitation - methods; Care and treatment; Catheters; CPR; Cytokines; Health aspects; Heart Arrest - genetics; Heart Arrest - metabolism; Heart Arrest - therapy; ICAM-1; Inflammation; Intercellular Adhesion Molecule-1 - metabolism; Ischemia; Male; Mice; Mutation; Original; Patient outcomes; Peroxidase - metabolism; Potassium; Rodents; Science; Signal transduction; Social interaction; TLR4; Toll-Like Receptor 4 - genetics; Toll-Like Receptor 4 - metabolism; Toll样受体4; Traumatic brain injury; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-TNF; Ventilation; 心肺复苏; 生存率; 突变小鼠; 缺血/再灌注损伤; 酶联免疫吸附试验; 预后; China; Cardiac Arrest; Cardiopulmonary Resuscitation; Cerebral Injury; Toll-like Receptor 4
• DOI: 10.4103/0366-6999.166024
• ISSN: 0366-6999; 2542-5641

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-l） 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 2 1.16％ in C3 H/HeJ group compared with 53.11％ in C3H/HeN group （P ＜ 0.05）.And there were significantly lower levels ofhippocampal TNF-α and MPO in C3H/HeJ mice （TNF-α：6.85±1.19 ng/mL,MPO：0.33±0.11 U/g） than C3 H/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 ofICAM-l was much lower in C3H/HeJ group than in C3H/HeN group after CPR （P ＜ 0.01）.Conclusion：TLR4 signaling is involved in brain damage and in inflammation triggered by CA/CPR.