Prognostic role of serum ammonia in patients with sepsis-associated encephalopathy without hepatic failure

Zhao, Lina; Hou, Shuxun; Na, Risu; Liu, Bin; Wang, Zhiwei; Li, Yun; Xie, Keliang

doi:10.3389/fpubh.2022.1016931

Cited by 3 publications

(4 citation statements)

References 29 publications

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“…7 h). Since there are no exact diagnostic criteria for SAE, we found that the Glasgow Coma Score (GCS), Sequential Organ Failure Assessment Score (SOFA), and Acute Physiology and Chronic Health Evaluation (APACHE II) score may be associated with SAE, and so we examined the correlation between TRIM45 and these indicators [ 34 – 37 ]. We analysed TRIM45 mRNA levels in peripheral blood monocytes and the APACHE II score, SOFA score in some patients with sepsis by linear regression analysis, and compare the level of TRIM45 in the two groups (group1: GCS score ≤ 8; group2: GCS score > 9) for patients with sepsis.…”

Section: Resultsmentioning

confidence: 99%

Section: Knockdown Of Trim45 Can Inhibit Pyroptosis and Improve Cogni...mentioning

confidence: 99%

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TRIM45 aggravates microglia pyroptosis via Atg5/NLRP3 axis in septic encephalopathy

Huang,

Ye,

Zhao

et al. 2023

J Neuroinflammation

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Background Neuroinflammation mediated by microglial pyroptosis is an important pathogenic mechanism of septic encephalopathy (SAE). It has been reported that TRIM45 is associated with tumours and inflammatory diseases. However, the role of TRIM45 in SAE and the relationship between TRIM45 and microglial pyroptosis are unknown. In this study, we found that TRIM45 played an important role in regulating microglial pyroptosis and the molecular mechanism. Methods SAE was induced by intraperitoneal injection of LPS in WT and AAV-shTRIM45 mice. BV2 cells were treated with LPS/ATP in vitro. Cognitive function was assessed by the Morris water maze. Nissl staining was used to evaluate histological and structural lesions. ELISA was used to dectect neuroinflammation. qPCR was used to detect the mRNA levels of inflammatory cytokines, NLRP3, and autophagy genes. Western blotting and immunofluorescence analysis were used to analyse the expression of the proteins. Changes in reactive oxygen species (ROS) in cells were observed by flow cytometry. Changes in mitochondrial membrane potential in BV2 cells were detected by JC-1 staining. Peripheral blood mononuclear cells were extracted from blood by density gradient centrifugation and then used for qPCR, western blotting and flow detection. To further explore the mechanism, we used the overexpression plasmids TRIM45 and Atg5 as well as siRNA-TRIM45 and siRNA-Atg5 to analyse the downstream pathway of NLRP3. The protein and mRNA levels of TRIM45 in peripheral blood mononuclear cells from sepsis patients were examined. Results Knocking down TRIM45 protected against neuronal damage and cognitive impairment in septic mice. TRIM45 knockdown inhibited microglial pyroptosis and the secretion of inflammatory cytokines in vivo and in vitro, which was mediated by NLRP3/Gsdmd-N activation. Overexpression of TRIM45 could activate NLRP3 and downstream proteins. Further examination showed that TRIM45 regulated the activation of NLRP3 by altering Atg5 and regulating autophagic flux. It was also found that overexpression and knockdown of TRIM45 affected the changes in ROS and mitochondrial membrane potential. Thus, knocking down TRIM45 could reduce microglial pyroptosis, the secretion of proinflammatory cytokines, and neuronal damage and improve cognitive function. In addition, the level of TRIM45 protein in septic patients was increased. There was a positive linear correlation between APACHE II score and TRIM45, between SOFA score and TRIM45. Compared to group GCS > 9, level of TRIM45 were increased in group GCS ≤ 8. Conclusion TRIM45 plays a key role in neuroinflammation caused by LPS, and the mechanism may involve TRIM45-mediated exacerbation of microglial pyroptosis via the Atg5/NLRP3 axis. Graphical Abstract

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Section: Resultsmentioning

confidence: 99%

Section: Knockdown Of Trim45 Can Inhibit Pyroptosis and Improve Cogni...mentioning

confidence: 99%

TRIM45 aggravates microglia pyroptosis via Atg5/NLRP3 axis in septic encephalopathy

Huang,

Ye,

Zhao

et al. 2023

J Neuroinflammation

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“…Alexandre et al found that blood ammonia levels >100 μmol/L were linked to intracranial hypertension and higher mortality [ 89 ]. Retrospectively analyzing 465 SAE patients admitted to the ICU, Zhao et al found that serum ammonia levels were linked to higher SOFA score and lactate level in SAE patients without liver failure [ 90 ]. SAPS II and Charlson scores were independent risk factors for death in SAE patients and could be used to assess their prognosis.…”

Section: Disorder Of Amino Acid Balancementioning

confidence: 99%

Research progress in the pathogenesis of sepsis-associated encephalopathy

Zhou,

Bai,

Tang

et al. 2024

Heliyon

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“…Serum ammonia is an important neurotoxic molecule, and elevated nonhepatic serum ammonia levels are commonly seen in patients with sepsis. Our previous research found that the serum ammonia level was associated with higher SOFA scores and lactate levels in patients with SAE [ 12 ]. However, the relationship between nonhepatic serum ammonia levels and incidence of SAE remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Relationship between Nonhepatic Serum Ammonia Levels and Sepsis-Associated Encephalopathy: A Retrospective Cohort Study

Wang,

Yan,

Shi

et al. 2023

Emergency Medicine International

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Objectives. Nonhepatic hyperammonemia often occurs in patients with sepsis. Ammonia plays an essential role in the occurrence of hepatic encephalopathy. However, the relationship between nonhepatic serum ammonia levels and sepsis-associated encephalopathy (SAE) remains unclear. Thus, we aimed to evaluate the association between serum ammonia levels and patients with SAE. Methods. Data of critically ill adults with sepsis who were admitted to the intensive care unit were retrieved from the Medical Information Mart for Intensive Care IV (MIMIC IV) between 2008 and 2019 and retrospectively analyzed. Data of patients with sepsis patients and serum ammonia not related to acute or chronic liver disease were not included. Results. Data from 720 patients with sepsis were included. SAE was found to have a high incidence (64.6%). After adjusting for other risk factors, a serum ammonia level of ≥45 μmol/L (odds ratio (OR): 3.508, 95% confidence interval (CI): 2.336–5.269, p < 0.001 ) was found to be an independent risk factor for patients with SAE; moreover, as the serum ammonia level increased, the hospital mortality of SAE gradually increased in a certain range (serum ammonia <150 μmol/L). Serum ammonia levels of ≥45 μmol/L were associated with higher Simplified Acute Physiology Score II and Sequential Organ Failure Assessment (SOFA) scores in patients with SAE. Besides, our study found that patients with SAE used opioid analgesics (OR:3.433, 95% CI: 1.360–8.669, p = 0.009 ) and the SOFA scores of patients with SAE (OR: 1.126, 95% CI: 1.062–1.194, p < 0.001 ) were significantly higher than those without SAE. Conclusions. Nonhepatic serum ammonia levels of ≥45 μmol/L evidently increased the incidence of SAE. Serum ammonia levels should be closely monitored in patients with sepsis.

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Prognostic role of serum ammonia in patients with sepsis-associated encephalopathy without hepatic failure

Cited by 3 publications

References 29 publications

TRIM45 aggravates microglia pyroptosis via Atg5/NLRP3 axis in septic encephalopathy

TRIM45 aggravates microglia pyroptosis via Atg5/NLRP3 axis in septic encephalopathy

Research progress in the pathogenesis of sepsis-associated encephalopathy

Relationship between Nonhepatic Serum Ammonia Levels and Sepsis-Associated Encephalopathy: A Retrospective Cohort Study

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