Abstract
Background: Sepsis- associated encephalopathy (SAE) is an early and common feature of severe infections. Oxidative stress is one of the mechanisms associated with the pathophysiology of SAE. The goal of this study was to investigate the involvement of NADPH oxidase in neuroinflammation and in the long-term cognitive impairment of sepsis survivors. Methods: Sepsis was induced in WT and gp91 phox knockout mice (gp91 phox�/� ) by cecal ligation and puncture (CLP) to induce fecal peritonitis. We measured oxidative stress, Nox2 and Nox4 gene expression and neuroinflammation in the hippocampus at six hours, twenty-four hours and five days post-sepsis. Mice were also treated with apocynin, a NADPH oxidase inhibitor. Behavioral outcomes were evaluated 15 days after sepsis with the inhibitory avoidance test and the Morris water maze in control and apocynin-treated WT mice. Results: Acute oxidative damage to the hippocampus was identified by increased 4-HNE expression in parallel with an increase in Nox2 gene expression after sepsis. Pharmacological inhibition of Nox2 with apocynin completely inhibited hippocampal oxidative stress in septic animals. Pharmacologic inhibition or the absence of Nox2 in gp91 phox�/� mice prevented glial cell activation, one of the central mechanisms associated with SAE. Finally, treatment with apocynin and inhibition of hippocampal oxidative stress in the acute phase of sepsis prevented the development of long-term cognitive impairment. Conclusions: Our results demonstrate that Nox2 is the main source of reactive oxygen species (ROS) involved in the oxidative damage to the hippocampus in SAE and that Nox2-derived ROS are determining factors for cognitive impairments after sepsis. These findings highlight the importance of Nox2-derived ROS as a central mechanism in the development of neuroinflammation associated with SAE.
Highlights
The project ‘HUPE against sepsis’ seeks to emphasize the importance of early recognition of sepsis, in order to accelerate the implementation of measures associated with decreased mortality for severe sepsis
The study group had greater probability to have a first dose of empirical antibiotic in less than 6 hours compared with the control group (RR 2.48; 95% cardiac index (CI) 1.88 to 3.26)
The aims of this study were to describe a population of cancer patients with severe pneumonia who required ICU admission; identify predictors of hospital mortality; and classify the study population based on ATS CAP/healthcare-associated pneumonia (HCAP) definitions providing a comparison of clinical data, microbiologic variables and outcomes between the two groups
Summary
The project ‘HUPE against sepsis’ seeks to emphasize the importance of early recognition of sepsis, in order to accelerate the implementation of measures associated with decreased mortality for severe sepsis. Materials and methods: To evaluate the reduction in time of antimicrobial adjustment therapy in patients with sepsis comparing a rapid molecular test (SeptiFast®) with conventional blood cultures, a randomized controlled clinical trial was conducted between October 2012 and May 2013 in a cardiology hospital. The aims of this study were to describe a population of cancer patients with severe pneumonia (not acquired in the hospital setting) who required ICU admission; identify predictors of hospital mortality; and classify the study population based on ATS CAP/HCAP definitions providing a comparison of clinical data, microbiologic variables and outcomes between the two groups. Materials and methods: As the diagnostic criteria of the systemic inflammatory response syndrome (SIRS) are very sensitive and very little specific, we selected patients with severe sepsis and septic shock in the first 24 hours of ICU admission, 18 years old or more, with two general and one or more inflammatory criteria of SIRS (ACCP/SCCM/2003).
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