BackgroundSepsis-associated encephalopathy (SAE) is a diffuse brain dysfunction caused by many pathological events, including neuroinflammation and oxidative stress damage. Increasing evidence suggests that parvalbumin (PV) interneurons play a key role in the cognitive process, whereas the dysfunction of these interneurons has been implicated in a number of major psychiatric disorders. Here, we aimed to investigate whether enhanced inflammation and oxidative stress-mediated PV interneuron phenotype loss plays a role in sepsis-induced cognitive impairments.MethodsMale C57BL/6 mice were subjected to cecal ligation and puncture or sham operation. For the interventional study, the animals were chronically treated with a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor, apocynin, at 5 mg/kg. The mice were euthanized at the indicated time points, and the brain tissues were harvested for determination of the PV, membrane subunit of NADPH oxidase gp91phox, and markers of oxidative stress (4-hydroxynonenal and malondialdehyde) and inflammation (tumor necrosis factor alpha (TNF-α), interleukin (IL)-1β, IL-6, and IL-10). A separate cohort of animals was used to evaluate the behavioral alterations by the open field and fear conditioning tests. Primary hippocampal neuronal cultures were used to investigate the mechanisms underlying the dysfunction of PV interneurons.ResultsSepsis resulted in cognitive impairments, which was accompanied by selective phenotype loss of PV interneurons and increased gp91phox, 4-hydroxynonenal, malondialdehyde, IL-1β, and IL-6 expressions. Notably, these abnormalities could be rescued by apocynin treatment.ConclusionSelective phenotype loss of PV interneurons, as a result of NADPH oxidase 2 (Nox2) activation, might partly contribute to cognitive impairments in a mouse model of SAE.
With the rapid development and application of the computer network technology, computer network system has brought many unsafe hidden dangers to the user. The computer network security has got more and more attentions of people. Therefore, this paper analyzes the main problems in computer network security and proposes some effective preventive measures. The author hopes these will help the computer network plays better role for people.
Exploration of low carbon city planning is the key to achieve sustainable development, which also has important meaning for the construction of energy-saving society. The value engineering theory was introduced into low carbon urban planning in this work, with the analysis method of three steps proposed. Firstly, sort out the planning index system and determine the key parameters. Secondly, quantify the value coefficient of each parameter by the expert scoring method. Lastly, get the highest priority value coefficient to achieve the purpose of carbon effect with lowest cost. Through illustrating the principle of the method by an example, the actual meaning of low carbon city planning using value engineering theory was proved effective.
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