Improved Survival and Neurological Outcomes after Cardiopulmonary Resuscitation in Toll-like Receptor 4-mutant Mice
- Author:
- No author available
- Journal Title:
- Chinese Medical Journal
- Issue:
- 19
- DOI:
- 10.4103/0366-6999.166024
- Key Word:
- Cardiac Arrest;Cardiopulmonary Resuscitation;Cerebral Injury;Toll-like Receptor 4
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-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.
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