The 25 Years of the Laboratory of Cell Pathology in Critical Conditions, V. A. Negovskiy Research Institute of General Reanimatology, Federal Scientific-Clinical Center for Reanimatology and Rehabilitation

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.

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7. Golubev A. M., Petrova M. V., Grechko A. V., Zakharenko V. E., Kuzovlev A. N., Ershov A. V. Molecular markers of ischemic stroke. General Reanimatology = Obshchaya Reanimatologiya. 2019; 15 (5): 11–22. (in Russ. &Eng.). DOI: 10.15360/1813-9779-2019-5-11-22.

8. Babkina A. S., Yadgarov M. Y., Ostrova I. V., et al. Serum levels of VEGF-A and its receptors in patients in different phases of hemorrhagic and ischemic strokes. Curr Issues Mol Biol. 2022; 44 (10): 4888-4901. DOI: 10.3390/cimb44100332.

9. Tynterova A. M., Shusharina N. N., Golubev A. M., Moiseeva E. M., Litvinova L. S. Linking immunological parameters and recovery of patient’s motor and cognitive functions in the acute period of ischemic stroke. General Reanimatology = Obshchaya Reanimatologiya. 2024; 20 (1): 4–14. (in Russ. &Eng.). DOI: 10.15360/1813-9779-2024-1-4-14.

10. Golubev A. M., Radutnaya M. L., Zakharenko V. E., Babkina A. S., Petrova M. V., Lyubomudrov M. A., Yadgarov M. Ya., et al. Biomarkers-predictors of mortality in patients with ischemic stroke. Physical and Rehabilitation Medicine, Medical Rehabilitation= Fizicheskaya i Reabilitatsionnaya Meditsina, Meditsinskaya Reabilitatsiya. 2023; 5 (4): 312–321. (In Russ.). DOI: 10.36425/rehab619331.

11. Babkina A. S., Baeva A. A., Bashirova A. R., Blagonravov M. L., Golubev A. M., Grebencchikov O. A., Grechko A. V. et al. Biological markers of damage and regeneration of the central nervous system: monograph. Moscow: VTsI, 2021: 431. ISBN 978-5-6044159-0-0. (in Russ.).

12. Babkina A. S., Lyubomudrov M. A., Golubev M. A., Pisarev M. V., Golubev A. M. Neuron-specific enolase-what are we measuring?. Int J Mol Sci. 2024; 25 (9): 5040. DOI: 10.3390/ijms25095040.

13. Golubev A. M. Enolases: Limitations for implementation in clinical practice (Clinical review). General Reanimatology = Obshchaya Reanimatologiya. 2024; 20 (3): 53–64. (in Russ. &Eng.).

14. Golubev A. M. Morphological classification of neuronal damage. General Reanimatology = Obshchaya Reanimatologiya. 2025; 21 (5): 4–14. (in Russ. &Eng.). DOI: 10.15360/1813-9779-2025-5-2580.

15. Golubev A. M., Lyubomudrov M. A., Babkina A. S., Tsokolayeva Z. I. Heterogeneity of NeuN protein distribution as a marker of morphological personalization of cerebral cortex neurons: an experimental study. General Reanimatology = Obshchaya Reanimatologiya. 2025; 21 (1): 55–61. (in Russ. &Eng.). DOI: 10.15360/1813-9779-2025-1-55-61.

16. Lyubomudrov M, Babkina A, Tsokolaeva Z, et al. Morphology of cortical microglia in the hyperacute phase of subarachnoid hemorrhage. Biology (Basel). 2024; 13 (11): 917. DOI: 10.15360/1813-9779-2025-1-55-61.

17. Moroz V. V., Golubev A. M. Classification of acute respiratory distress syndrome. General Reanimatology = Obshchaya Reanimatologiya. 2007; 3 (6): 7–9. (in Russ. &Eng.). DOI: 10.15360/1813-9779-2007-6-7-9.

18. Moroz V. V., Churlyaev Yu. A., Kiselev V. V., Sitnikov P. G., Redkokasha L. Yu. Features of gas exchange and mechanical properties of the lungs in miners with severe concomitant injury. General Reanimatology = Obshchaya Reanimatologiya. 2007; 3 (6): 10–13. (in Russ. &Eng.). DOI: 10.15360/1813-9779-2007-6-10-13.

19. Golubev A. M., Moroz V. V., Sundukov D. V. Pathogenesis of acute respiratory distress syndrome. General Reanimatology = Obshchaya Reanimatologiya. 2012; 8 (4): 13. (in Russ. &Eng.). DOI: 10.15360/1813-9779-2012-4-13.

20. Vlasenko A. V., Golubev A. M., Alekseev V. G., Bulatov N. N., Evdokimov E. A. Mechanisms of pathogenesis, diagnosis, and treatment of acute respiratory distress syndrome. Part I. Medical Alphabet=Meditsinskiy Alfavit. (in Russ.). 2017; 1 (5): 5–13.

21. Moroz V. V., Golubev A. M., Kuzovlev A. N., Pisarev V. M., Shabanov A. K., Golubev M. A. Surfactant protein D is a biomarker of acute respiratory distress syndrome. General Reanimatology = Obshchaya Reanimatologiya. 2013; 9 (4): 11. (in Russ. &Eng.). DOI: 10.15360/1813-9779-2013-4-11.

22. Perepelitsa S. A. Acute respiratory distress syndrome in preterm newborns (Morphological Study). General Reanimatology = Obshchaya Reanimatologiya. 2020; 16 (1): 35–44. (in Russ. &Eng.). DOI: 10.15360/1813-9779-2020-1-35-44.

23. S. A. Perepelitsa, A. M. Golubev, and V. V. Moroz. Preterm neonate: a monograph. Moscow: First Economic Publishing House; 2019. (in Russ.).

24. Tynterova A. M., Perepelitsa S. A., Skalin Yu. E., Reverchuk I. V., Tikhonova O. A., Grishina A. A. Neuropsychological diagnosis in the acute period of ischemic stroke. V. M. Bekhterev Review of Psychiatry and Medical Psychology=Obozrenie Psikhiatrii i Meditsinskoy Psikhologii imeni V. M. Bekhtereva. 2022; 56 (1): 54 С. А.62. (in Russ.). DOI: 10.31363/2313-7053-2022-56-1-54-62.

25. Tynterova A., Perepelitsa S., Golubev A. Personalized neurophysiological and neuropsychological assessment of patients with left and right hemispheric damage in acute ischemic stroke. Brain Sci. 2022; 12 (5): 554. DOI: 10.3390/brainsci12050554.

26. Tynterova A. M., Moiseeva E. M., Golubev A. M., Shusharina N. N. The role of endothelinergic and nitroxidergic reactions in predicting the functional outcome in patients with ischemic stroke of different severity. General Reanimatology = Obshchaya Reanimatologiya. 2023; 19 (5): 13–20. (in Russ. &Eng.). DOI: 10.15360/1813-9779-2023-5-2354.

27. Grechko A. V., Moroz V. V., Golubev A. M., Kuzovlev A. N., Grebenshchikov O. A., Shabanov A. K., Gabitov M. V., et al. Personalization in critical care medicine. Moscow: Advanced Solutions; 2024: 248. (In Russ.).

28. Babkina A. S. The role of infectious diseases of the lower respiratory tract in the pathogenesis of ischemic stroke (Review). General Reanimatology = Obshchaya Reanimatologiya. 2025; 21 (5): 59–72. (in Russ. &Eng.). DOI: 10.15360/1813-9779-2025-5-2598.

29. Babkina A. S., Yadgarov M. Y., Lyubomudrov M. A., et al. Morphologic findings in the cerebral cortex in COVID-19: association of microglial changes with clinical and demographic variables. Biomedicines. 2023; 11 (5): 1407. DOI: 10.3390/biomedicines11051407.

30. Babkina A. S., Yadgarov M. Y., Volkov A. V., Kuzovlev A. N., Grechko A. V., Golubev A. M. Spectrum of thrombotic complications in fatal cases of COVID-19: focus on pulmonary artery thrombosis in situ. Viruses. 2023; 15 (8): 1681. DOI: 10.3390/v15081681.

31. Babkina A. S., Ostrova I. V., Yadgarov M. Y.,Kuzovlev A. N., Grechko A. V., Volkov A. V., Golubev A. M. The role of Von Willebrand factor in the pathogenesis of pulmonary vascular thrombosis in COVID-19. Viruses. 2022; 14 (2): 211. DOI: 10.3390/v14020211. PMID: 35215805.

32. Babkina A. S., Pisarev M. V., Grechko A. V., Golubev A. M. Arterial thrombosis in acute respiratory infections: an underestimated but clinically relevant problem. J Clin Med. 2024; 13 (19): 6007. DOI: 10.3390/jcm13196007.

33. Potapov A. F., Golubev A. M., Matveyev A. S. Surgical abdominal infection: state of the problem and modern strategy of antibacterial therapy. Yakutsk: NEFU; 2011: 120. ISBN 978-5-7513-1509-2. (in Russ.).

34. Perepelitsa S. A., Moroz V. V., Golubev A. M. Infections of the neonatal period. Moscow: Advanced Solutions; 2021. ISBN 978-5-6044549-8-5. (in Russ.).

35. A method for treating poisoning caused by organophosphorus substances. Golubev A. M., Magomedov M. A., Dalgatov G. D., Ragimova D. M. Patent for invention RU 2155583 C2. 10.09.2000. (in Russ.).

36. Basarab D. A., Kozhura V. L., Golubev A. M., Timkina M. I., Moroz V. V. Effects perftoran on experimental acute intestinal ischemia. Russian Journal of Anaesthesiology and Reanimatology=Anesteziologiya i Reanimatologiya. 2002; 6: 31–36. (in Russ.). PMID: 12611154.

37. Kozhura V. L., Basarab D. A., Timkina M. I., Golubev A. M., Reshetnyak V. I., Moroz V. V. Reperfusion injury after critical intestinal ischemia and its correction with perfluorochemical emulsion «perftoran». World J Gastroenterol. 2005; 11 (45): 7084–7090. (in Russ.). DOI: 10.3748/wjg.v11.i45.7084. PMID: 16437652.

38. Alkadarskii A. S., Golubev A. M. Correction of hypoxic lesions of cerebral cortical neurons with blood-substituting solutions in acute massive blood loss in the experiment. Russian Journal of Anaesthesiology and Reanimatology=Anesteziologiya i Reanimatologiya. 2004; 6: 49–51. (in Russ.). PMID: 15717521.

39. A method for detecting perfluorane/»perftoran» in biological tissues and liquid media. Ragimov R. M., Alkadarsky A. S., Golubev A. M. Patent for the invention RU 2221246 C2, 10.01.2004. Application No. 2001106753/15, dated 12.03.2001. (in Russ.).

40. Golubev A. M., Ragimov R. M., Osmanov A. O. Use of ozonated perfluorane in acute peritonitis. General Reanimatology = Obshchaya Reanimatologiya. 2005; 1 (1): 9–12. (in Russ. &Eng.). DOI: 10.15360/1813-9779-2005-1-9-12.

41. Emulsion of organofluorine compounds with oxygen-carrier properties. Feyzulova R. K. G., Khromov A. V., Kalinichenko A. N., Vorozhtsov G. N., Khan I. G., Moroz V. V., Golubev A. M., et al. Patent for invention RU 2469714 C1, 20.12.2012. Application No. 2011129373/15 dated 15.07.2011. (in Russ.).

42. Romanova O. L., Sundukov D. V., Blagonravov M. L., Barinov E. Kh., Golubev A. M. Expert assessment of pathological changes in internal organs in cases of clozapine and clozapine/ethanol poisoning. Moscow: Prospekt, 2022. ISBN 978-5-392-36634-7. (in Russ.).

43. Babkina A. S., Ryzhkov I. A., Antonova V. V., Tsokolayeva Z. I., Asanov A. R., Kalabushev S. N., Zarzhetsky Yu. V. Morphological and functional alterations in the cardiovascular system during acute clozapine poisoning (experimental study). General Reanimatology = Obshchaya Reanimatologiya. 2019; 15 (4): 67–75. (in Russ. &Eng.). DOI: 10.15360/1813-9779-2019-4-67-75.

44. Ryzhkov I. A., Babkina A. S., Tsokolayeva Z. I., Kalabushev S. N., Antonova V. V., Sergeeva M. V., Ershov A. V. Morphology and function of myocardium and skin microcirculation 24 hours after clozapine poisoning. General Reanimatology = Obshchaya Reanimatologiya. 2020; 16 (5): 56–64. (in Russ. &Eng.). DOI: 10.15360/1813-9779-2020-5-56-64.

45. Babkina A., Khadzhieva M., Ostrova I., Ryzhkov I., Golubev A. Global DNA methylation of brain neurons in acute poisoning with clozapine and its combination with alcohol: An experimental study. Russian Open Medical Journal. 2021; 10 (3). DOI: 10.15275/rusomj.2021.0306.

46. Romanova O. L., Sundukov D. V., Golubev M. A., Blagonravov M. L., Ershov A. V. Lung histopathology in baclofen poisoning. General Reanimatology = Obshchaya Reanimatologiya. 2021; 17 (2): 37–44. (in Russ. &Eng.). DOI: 10.15360/1813-9779-2021-2-37-44.

47. Bashirova A. R., Sundukov D. V., Babkina A. S., Golubev M. A., Telipov I. N. Morphometry of cortical neurons in acute clozapine and ethanol poisoning. General Reanimatology = Obshchaya Reanimatologiya. 2020; 16 (6): 19–30. (in Russ. &Eng.). DOI: 10.15360/1813-9779-2020-6-19-30.

48. A method for determining the time of a person’s death. Babkina A. S., Golubev A. M., Sundukov D. V., Ryzhkov I. A., Palyshev I. P., Tsokolayeva Z. I., Kuzovlev A. N. Patent for invention RU 2696847 C1, 06.08.2019. Application No. 2018146578, dated 26.12.2018. (in Russ.).

49. Babkina A. S., Sundukov D. V., Golubev A. M., Ryzhkov I. A., Tsokolayeva Z. I., Zarzhetsky Yu. V. Determination of the fluorescence intensity of coenzymes NADH and FAD in the skeletal muscle of the rat, depending on the post-mortem interval. Forensic Medical Expertise=/Sudebno-Meditsinskaya Ekspertisa. 2020; 63 (1): 31–35. (in Russ.). DOI: 10.17116/sudmed20206301131.

50. Babkina A. S., Sundukov D. V., Golubev A. M. The forensic implications of the relationship between the proteolytic enzymes activity and the changes in NADH and FAD fluorescence intensity in skeletal muscle when determining the time of death (Experimental Study). Forensic Medical Expertise=/Sudebno-Meditsinskaya Ekspertisa. 2021; 64 (3): 24–28. (in Russ.). DOI: 10.17116/sudmed20216403124.