Objectives. The goal is to study the effect of lithium chloride on the intensity of endotheliocytes apoptosis in a monolayer in vitro under the action of blood serum of patients with the syndrome of systemic inflammatory response in severe multiple trauma. Materials and methods. We used toxic blood serum of 5 patients with severe multiple trauma. As controls we used blood serum of 5 healthy donors. In different series of the experiment EA.hy926 endothelial cells were incubated with blood serum of a healthy person (control), with blood serum of patients with systemic inflammatory response syndrome in severe multiple trauma. Lithium chloride was added to the cell samples at final concentrations of 0.01, 0.1, 1, 10 mmol/L. After incubation the cells were removed with trypsin-versen solution fixed with 70 % ethanol and stained with propidium iodide. Cells containing fragmented genomic DNA were analyzed by flow cytometry. Results. It was revealed that toxic serum suppressed GSK-3p phosphorylation in endotheliocytes and also caused the splitting of VE-cadherin, a decrease in the amount of claudine and actin, initiating the destruction of intercellular contacts of the endothelial monolayer and apoptosis of endotheliocytes. Incubation of a monolayer of endotheliocytes with lithium chloride at a concentration of 1.0 mmol/l and higher almost completely prevented the dismantling of claudine, actin and VE-cadherin, and also reduced the intensity of apoptosis of endotheliocytes by more than 2 times. It was found that preincubation with lithium chloride at a concentration of 1 mmol/L not only prevented the inactivation of GSK-Зр, but even stimulated its phosphorylation. Conclusion. Lithium chloride prevents the dismantling of claudine and VE-cadherin in the intercellular contacts, reduces the number of apoptotic cells in the monolayer of the endothelial cells of the EA.hy926 line under the action of the blood serum of patients with a systemic inflammatory response syndrome in severe multiple trauma, which may indicate a protective effect of the drug on endothelial barrier. The results of this investigation suggest that the protective effect of lithium chloride on endothelium is realized via GSK-3p phosphorylation.
Background. The syndrome of systemic inflammatory response, which underlies the damaging effect of factors of infectious and non-infectious genesis, may cause multiple organ failure. The degree of its severity is determined, among other things, by the activation of neutrophils. The paper highlights new mechanisms of the anti-inflammatory action of the inhalation anesthetic xenon, mediated by a decrease in the ability of neutrophils to pro-inflammatory response.Aim of study. To evaluate the effect of xenon on the activation of human neutrophils under ex vivo conditions.Material AND methods. We studied the effect of xenon inhalation on reduction of the ability of neutrophils to be activated proinflammatory by reduced expression of adhesion molecules CD11b and CD66b on the surface of neutrophils and on the phosphorylation of proinflammatory kinases: ERK 1/2 and kinase — p38 in neutrophils of healthy volunteers.Results. The use of xenon at a dose of 30 vol. % within 60 minutes in healthy volunteers statistically significantly reduces the ability of neutrophils to proinflammatory activation. The addition of lipopolysaccharide (LPS) to the incubation medium of neutrophils causes their pronounced activation, statistically significantly increasing the phosphorylation of key proinflammatory neutrophil kinases ERK1/2 and kinase p38. Inhalation of xenon in volunteers (30% within 60 minutes) has a pronounced anti-inflammatory effect on LPS-stimulated neutrophils, decreasing their activation by inhibiting pro-inflammatory kinase ERK1/2 and pro-inflammatory MAP kinase p38.Conclusion. The actual study, performed on isolated neutrophils from volunteers who underwent xenon inhalation, revealed the anti-inflammatory properties of the inert gas xenon, which, in our opinion, may have a direct relationship to the identification of the mechanism of its neuroprotective properties. Thus, the research results available today suggest that xenon has a pronounced pleiotropic mechanism of brain protection. This is a partial blockade of NMDA receptors, and phosphorylation of the enzyme glycogen synthase-3β, and limitation of the inflammatory activation of neutrophils.Findings. Inhalation of xenon in volunteers (30% within 60 minutes) has a pronounced anti-inflammatory effect on neutrophils stimulated by lipopolysaccharides, decreasing their activation by inhibiting proinflammatory ERK 1/2 kinase and proinflammatory MAP kinase p38, as well as reducing the expression of markers of activation and degranulation CD11b and CD66b on the surface of neutrophils. Stimulation by lipopolysaccharides statistically significantly reduces spontaneous apoptosis of neutrophils, while xenon increases the ability of neutrophils to apoptosis, which is likely to contribute to the resolution of inflammation.
In addition to high mortality, craniocerebral injuries have another danger, a long rehabilitation period and a high percentage of disability with the development of cognitive impairment. This is primarily associated with the processes of neuroinflammation, which development, according to recent data, leads to a long-term impairment of consciousness. The anti-inflammatory effects of xenon inhalation anesthetic, which have been repeatedly shown in previous studies, have the potential to beneficially affect the level of consciousness in these patients by targeting key links of neuroinflammation.AIM OF STUDY To evaluate the effect of oxygen-xenon mixture inhalation on the level of consciousness recovery and the severity of spastic activity in patients after traumatic brain injury.MATERIAL AND METHODS A prospective randomized clinical trial of the effect of inhaled xenon sedation on the level of consciousness and spastic activity in patients with post-coma long-term impairment of consciousness was conducted. Patients were randomized into two equal groups. In group I (comparisons, n=15) (in addition to the standard treatment after a traumatic brain injury), each patient included in the study underwent 7 sessions of inhalation of an air-oxygen mixture with an oxygen content of at least 30 vol% for 30 minutes. In group II (study, n=15) (in addition to standard treatment), each patient included in the study inhaled an oxygen-xenon gas mixture (xenon content 30 vol%) for 7 days 1 time per day. Before and after the course of treatment (on the 7th day), patients were assessed using the CRS-R scale and the modified Ashworth scale.RESULTS The final evaluation included 12 patients from the comparison group and 12 patients from the study group. Three patients were excluded from each group as a result of critical incidents not related to the type of the therapy. In the comparison group on the 7th day, the level of consciousness was score 9 [7; 11] and did not differ statistically significantly from the baseline (p>0.05), which was score 8 [6; 10]. Spastic activity also did not change statistically significantly. In group II, the initial level of consciousness was 9 [7; 10], and on the 7th day — score 15 [12; 17], which was statistically significantly higher both in relation to the level of consciousness by the 1st day (p=0.021) within the group, and in relation to it on the 7th day in group I (p=0.038). When comparing spastic activity on the 1st and 7th days, we did not obtain a statistically significant difference in any of the groups.CONCLUSION Our method of xenon inhalation made it possible to have a beneficial effect on the level of consciousness of patients after traumatic brain injury, but this did not affect the final level of spastic activity in any way.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.