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.