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Revyakina D.N., Kharitonova O.V., Pozdnyakov D.I., Shabanova N.B., Gerashchenko A.D.
Characteristics of mitochondrial dysfunction in cerebral ischaemia of various aetiologies in the context of potential neuroprotective therapy
Keywords: cerebral ischemia, mitochondrial dysfunction, regression analysis, neuroprotection
Mitochondrial dysfunction is one of the factors involved in the pathogenesis of cerebral ischaemia. The extent of mitochondrial dysfunction varies considerably depending on the nature of ischaemic damage, which may influence not only the course of the disease but also the success of pharmacotherapy, for example with neuroprotective agents. The aim of the study was to search for relevant quantitative biomarkers of mitochondrial dysfunction in conditions of cerebral ischemia of various origins for rational selection and development of neuroprotective agents. Materials and methods. Cerebral ischemia was modeled in Wistar rats. Focal cerebral ischemia was induced by irreversible right-sided occlusion of the middle cerebral artery. Subtotal ischemia was reproduced by ligation of the right common carotid artery. In 72 hours, the rats were assessed for changes in the size of the necrosis zone, as well as the intensity of aerobic/anaerobic respiration, the activity of citrate synthase and succinate dehydrogenase, the content of ATP and cytochrome C. The dependence of changes in the necrosis zone on mitochondrial function indicators was assessed during regression analysis. Results. During the study, it was established that formation of a necrotic focus is noted in animals with both focal and subtotal ischemia. At this, in rats with focal ischaemia, the area of cerebral necrosis was larger than in animals with subtotal ischemia. Also, both variants of cerebral ischemia led to the development of mitochondrial dysfunction, which was expressed in a decrease in aerobic metabolism, activation of anaerobic processes, a decrease in the activity of mitochondrial enzymes and the release of pro-apoptotic cytochrome C. The regression equations obtained made it possible to establish that in animals with focal ischemia, the change in the necrosis zone is more dependent on the activity of citrate synthase (R2 = 0.7551; AIC = 4.6684), whereas in rats with subtotal ischemia, formation of the infarction zone depends most on the level of aerobic respiration (R2 = 0.9553; AIC = 2.1014). Conclusions. The results obtained suggest that in conditions of focal ischemia, formation of a necrosis zone is more dependent on the activity of citrate synthase and, accordingly, mitochondrial neoplasms. In subtotal ischemia, cerebral necrosis is closely related to the activity of aerobic metabolic processes. These differences in manifestation of mitochondrial dysfunction can serve as the basis for a rational choice of a preclinical model of cerebral ischemia when investigating new neuroprotective compounds.
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About authors
- Revyakina Daria N.
- 6th year Student, Specialty "Medical Biochemistry", Pyatigorsk Medical and Pharmaceutical Institute, Russia, Pyatigorsk (revyakinadaria@yandex.ru; ORCID: https://orcid.org/0009-0009-9578-0460)
- Kharitonova Olga V.
- Candidate of Biological Sciences, Associate Professor, Department of Biological Chemistry, Pyatigorsk Medical and Pharmaceutical Institute, Russia, Pyatigorsk (incentra@mail.ru; ORCID: https://orcid.org/0000-0001-7840-9269)
- Pozdnyakov Dmitry I.
- Candidate of Pharmaceutical Sciences, Associate Professor, Head of Department of Pharmacology with a course in Clinical Pharmacology, Pyatigorsk Medical and Pharmaceutical Institute, Russia, Pyatigorsk (pozdniackow.dmitry@yandex.ru; ORCID: https://orcid.org/0000-0002-5595-8182)
- Shabanova Natalia B.
- Candidate of Pharmaceutical Sciences, Associate Professor, Department of Pharmacology with a course of Clinical Pharmacology, Pyatigorsk Medical and Pharmaceutical Institute – Branch of the Volgograd State Medical University, Russia, Pyatigorsk (vahlushina@mail.ru; ORCID: https://orcid.org/0000-0002-7693-5182)
- Gerashchenko Anastasia D.
- Candidate of Pharmaceutical Sciences, Associate Professor, Department of Pharmacology with a course of Clinical Pharmacology, Pyatigorsk Medical and Pharmaceutical Institute – Branch of the Volgograd State Medical University, Russia, Pyatigorsk (anastasia_gerashchenko@mail.ru; ORCID: https://orcid.org/0000-0003-0294-2926)
Article link
Revyakina D.N., Kharitonova O.V., Pozdnyakov D.I., Shabanova N.B., Gerashchenko A.D. Characteristics of mitochondrial dysfunction in cerebral ischaemia of various aetiologies in the context of potential neuroprotective therapy [Electronic resource] // Acta medica Eurasica. – 2026. – №1. P. 34-43. – URL: https://acta-medica-eurasica.ru/en/single/2026/1/4/. DOI: 10.47026/2413-4864-2026-1-34-43.