Ischemic stroke remains one of the leading causes of mortality and long-term disability worldwide, and existing treatments are bounded by narrow therapeutic windows and low efficacy. Inert gases, particularly argon, have recently emerged as promising neuroprotectors capable of modulating the cellular response to ischemia. However, the analysis of their effects at the systemic, tissue, and cellular levels remains incomplete.

The aim of the study was to provide an comprehensive assessment of the neuroprotective properties of argon in vitro and in vivo using the focal cerebral ischemia model in rats .

Materials and methods. A two-stage experimental study was conducted, combining in vivo and in vitro approaches. In vivo, focal ischemic stroke was induced in rats using a model of photochemically initiated thrombosis. The animals with induced stroke were divided into two groups based on inhalation mixture composed of N₂ 70% / O₂ 30% (comparison group I + iN₂, n = 10) and Ar 70% / O₂ 30% (main group I + iAr, n = 10). Additionally, 3 groups were included in the experiment: sham-operated animals (SO, n = 6), subjected to sham surgery without stroke induction, and 2 groups of intact animals receiving three inhalations of studied gas mixtures: Int. + iN₂ , n = 7; Int. + iAr, n = 5. Neurological outcomes were studied in a longitudinal mode, followed by a quantitative assessment of the infarction volume based on MRI data, histological and immunohistochemical analyses (GFAP, Iba-1, S100b, caspase-3, von Willebrand factor, etc.), and quantification of marker proteins involved in the regulation of signaling pathways (Akt/GSK-3, Nrf2, NFκB, IL-1α, IL-6, caspase-3) using western blotting. In vitro cultures of neuronal (SH-SY5Y), glial (C6), and endothelial (Ea.Hy926) cells were incubated in an argon-oxygen medium for 24 hours. Functional studies of cultures included assessment of mitochondrial transmembrane potential and lysosomal activity using confocal microscopy.

Results. In an in vivo experiment, argon significantly reduced the volume of damage according to MRI data (I + iN2 21.5 ± 5.9 mm³ vs I + iAr 12.5 ± 4.3 mm³, p = 0.0078), improved neurological recovery (I + N₂ and I + iAr group: on the 3[rd] (7.5 (4.2; 10.2) vs 10.0 (10.0; 12.0), p = 0.0015), 7[th] (8.0 (6.7; 9.2) vs 10.0 (9.0; 12.2), p = 0.038) and 14[th] days of the study (4.5 (2.7; 7.2) vs 12.0 (10.7; 12.2), p = 0.0008), It preserved significant neuronal density in the penumbra ( p = 0.001), and downregulated astroglia and microglia activation. In addition to a significant decrease in caspase-3 expression (p = 0.002) and modulation of pro-inflammatory cytokines (Ila was significantly lower in the I + iAr group, p = 0.002), there was an apparent activation of cytoprotective signaling pathways (Akt (p = 0.006) and Nrf2 (p = 0.019)). In vitro , argon exposure increased the proportion of high-potential mitochondria in neuronal (p = 0.01) and glial cells (p < 0.0001), and significantly stimulated lysosomal activity in endothelial cells (p = 0.0006).

Conclusion. This comprehensive study demonstrates that argon has a pronounced neuroprotective effect in a model of ischemic brain damage, manifesting by reduction of ischemic lesion volume, improvement in neurological status, and modulation of key molecular and cellular mechanisms of damage. The results demonstrate that argon activates protective mechanisms both in vivo and vitro. Therefore, argon can be considered as a promising and safe candidate for further preclinical and clinical studies in the field of neuroprotective therapy.

The laboratory of cell pathology in critical conditions (LCPCC) at the V. A. Negovskiy Research Institute of General Reanimatology, Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, celebrated its 25^th anniversary in 2025. Since its inception, the LCPCC has been headed by Dr. A. M. Golubev, Doctor of Medical Sciences (MD/PhD), Professor, Honored Scientist of the Russian Federation, Honored Scientist of the Republic of Dagestan, Honored Worker of Science and High Technology of the Russian Federation, and laureate of the Russian Federation Government Prize in Science and Technology.

Objective of the review: based on the analysis of the main results of scientific activities of the LCPCC, to show the prospects for research in the field of general pathology of critical conditions.

Materials and methods. The analysis of scientific activities of the LCPCC included 50 sources, including 6 books and monographs, 4 patents, and 39 articles.

Results. The main data obtained on 10 research topics are presented: 1. Post-resuscitation changes in the brain at the level of neuronal populations. 2. The relationship between molecular and cellular markers of damage and recovery of the central nervous system (CNS) with general pathological processes in acute cerebrovascular events. 3. The role of molecular and cellular markers of the central nervous system, detected through biochemical and immunohistochemical methods from the standpoint of general pathology. 4. Development and improvement of methods for diagnosis and treatment of acute respiratory distress syndrome. 5. Implementation of personalized medicine principles in fundamental and clinical research. 6. Pathogenesis of fatal complications of acute infectious diseases of the lower respiratory tract. 7. Pathogenesis of complications of infectious disease in critical conditions. 8. Properties of perfluorocarbon emulsions in experiment. 9. Pathogenesis of acute poisoning with neuroleptics in combination with alcohol. 10. Markers of postmortem changes in tissue metabolism for the development of new methods for determining the time of death.

Conclusion. The current level of development of reanimatology and intensive care has led to the emergence of a category of patients in long-term critical conditions. One of the key tasks of the LCPCC is expanding knowledge in the field of general pathology of long-term critical illness. Since the topics of research in this field are multidisciplinary in nature, the efficacy of achieving the stated goal is ensured through close cooperation with biologists, clinicians, pathologists, and forensic experts.

The aim of this study is to determine the prevalence of antibiotic resistance genetic markers in pathogens causing lower respiratory tract infections in patients with chronic critical illness.

Materials and Methods. We analyzed genetic markers of resistance to antimicrobial agents in pathogens causing lower respiratory tract infections in 251 patients in a chronic critical condition who were admitted to the intensive care unit (ICU) in 2025. Pathogen identification and gene detection were performed using an automated analyzer and the real-time polymerase chain reaction (qPCR) method.

Results. The predominance of three pathogens — Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa — was confirmed; these accounted for more than 40% of the identified infections. It was found that among the identified genetic determinants of resistance, the shv gene (58.35%) was predominant; this gene is responsible for the intrinsic resistance of K. pneumoniae and the acquired resistance of E. coli. The ctx-m-1 gene ranked second in prevalence at 55.80 %, and the tem gene ranked third at 50.29 %. Carbapenemase genes accounted for a significant proportion: ndm genes were detected in 41.45 % of samples, and genes of the oxa family were widely distributed — oxa-48-like was detected in 40.47 % of cases, oxa-40-like in 38.51 %, oxa-51-like in 34.38 %, and oxa-23-like in 18.86 %.

Conclusion. Among patients with chronic critical illness admitted to the ICU, Gram-negative bacteria — including Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa — were the predominant pathogens causing lower respiratory tract infections in more than 40 % of cases. Two or more genetic markers of resistance were detected in 80.55% of the samples. The oxa- 51-like gene was detected in all A. baumannii strains. Carbapenemase genes (ndm, oxa, kpc) and beta-lactamase genes (shv, ctx-m-1, tem) were prevalent.

Aim of the study: to compare the capabilities of light microscopy and atomic force microscopy (AFM) in assessing the morphological features of red blood cell (RBC) damage.

Materials and Methods. The study used blood from three healthy male donors with a mean age of 36 ± 5 years. RBCs were incubated with a hemin solution for 60 minutes. After incubation, blood smears were prepared. Morphological analysis was performed using an Olympus CX41 light microscope. The RBC topography was assessed using AFM on an NTEGRA BIO instrument in semi-contact mode. The distribution of morphological forms, cell diameter, and cell height were analyzed.

Results. A predominance of discocytes was observed in the control group, using both methods (light microscopy — 94 ± 2 %, AFM — 94 ± 1 %). After exposure to hemin 96 ± 2 % of the cells lost their central pallor and were classified as planocytes according to light microscopy. However, AFM revealed that these cells were spheroechinocytes (98 ± 1 %), characterized by a decrease in diameter from 7.6 ± 0.6 μm to 5.9 ± 0.4 μm (p = 0.008), an increase in height from 356 ± 22 nm to 737 ± 148 nm (p = 0.047), and the presence of multiple protrusions on the membrane.

Conclusion. Light microscopy reveals the loss of central pallor but does not allow for verification of the true three-dimensional shape of the damaged cells. AFM is necessary to refine the morphological classification and to quantitatively assess height and diameter. Thus, light microscopy is suitable for initial screening, while AFM is suitable for detailed assessment of RBC morphological alterations. 

Acute massive blood loss and hemorrhagic shock in severe trauma remain the leading causes of preventable mortality. Despite the impactfull significance of clinical studies, experimental modeling in laboratory animals remains an indispensable for fundamental studies on the pathophysiology of trauma and hemorrhagic shock, as well as for the initial assessment of the efficacy and safety of therapeutic interventions.

The purpose of this review is to systematize current approaches to the experimental modeling of blood loss, trauma, and hemorrhagic shock, as well as to identify the key factors that determine the translational potential of preclinical studies.

Materials and Methods. We conducted an analysis of domestic and international publications available in the PubMed, Scopus, Web of Science, Google Scholar, and eLIBRARY databases, focusing on experimental models of hemorrhagic shock, including classical and modern approaches to their reproduction, the selection of laboratory animals, and the bioethical aspects of conducting research. Based on the search results, we reviewed 1,819 sources, of which 106 were include

Results. We identified the main types of experimental models of hemorrhagic shock: volume-controlled, blood pressure-controlled, and uncontrolled blood loss models. We demonstrated that the choice of model is determined by the research objectives and requires a balance between standardization, reproducibility, and clinical relevance. A comparative analysis of various types of laboratory animals was conducted to demonstrate differences in their physiology, immune responses, and coagulation reactions affecting the interpretation of results. Key bioethical 3R principles, requirements for anesthesiological care, monitoring, and the selection of study endpoints were discussed in the review.

Conclusion. The translational potential of experimental models is determined by the alignment of the protocol with the study objectives, the appropriate selection of the laboratory model, the standardization of the blood loss procedure, compliance with bioethical requirements, and the use of clinically relevant endpoints. Promising areas for further research include improving the external validity of the models, multicenter preclinical validation of protocols, and the implementation of digital tools for analyzing experimental data.

According to the current concept, sepsis is a life‑threatening multi‑organ dysfunction resulting from a dysregulated host immune response to infection. Existing models regarding the causes and mechanisms of sepsis development overlook the role of pathobiota metabolism.

The aim of the study is to focus on the etiological and pathogenetic significance of pathobiota in the development of metabolic disorders, energy deficiency, and organ dysfunction during sepsis, and to substantiate the rationale for a metabolomic approach to monitoring critical conditions and antimicrobial therapy for sepsis.

Materials and methods. Analysis of literature data and synthesis of clinical and experimental research results from recent years, including the authors’ own findings.

Results. We presented a concept of sepsis in which the metabolites of the pathobiota were considered as direct mediators of metabolic stress, systemic inflammation, mitochondrial and organ dysfunction. Five tenets of the authors’ concept demonstrate that a metabolomic approach to studying sepsis makes it possible to explain the actual contribution of bacteria to the development of multiple organ failure, regardless of the presence or absence of documented bacteremia and local foci of infection. Alongside the theoretical rationale of the concept of sepsis based on clinical data, the authors presented results from experimental studies on immune response dysregulation associated with altered microbial tryptophan metabolism, and the effects of microbial intermediate metabolites on cyclooxygenase activity and inflammatory signaling. Evidence was provided regarding the involvement of aromatic microbial metabolites in mitochondrial dysfunction and the role of acetyl phosphate in sepsis, with particular attention paid to the metabolic reprogramming of the pathobiota.

Conclusion. The author’s concept of sepsis makes it possible to substantiate and initiate the search for new diagnostic and therapeutic targets aimed at the specific modulation of pathobiota metabolism, which will contribute to the survival of patients at high risk of a fatal outcome.