transmedТрансляционная медицинаTranslational Medicine2311-44952410-5155Almazov National Medical Research Centre, Saint Petersburg, Russia10.18705/2311-4495-2024-11-1-87-102EYWTGTtransmed-847Research ArticleНЕВРОЛОГИЯNEUROLOGYПатогенетические сценарии развития ишемии головного мозга и основные элементы ишемического каскадаPathogenetic scenarios of the development of brain ischemia and the main elements of the ischemic cascadehttps://orcid.org/0000-0002-1002-9419ШиленкоЛ. А.ShilenkoL. A.

Леонид Алексеевич Шиленко, ординатор 1 года обучения, лаборант-исследователь

кафедра факультетской терапии с клиникой; НИЛ патологии малого круга кровообращения

197341; ул. Аккуратова, д. 2; Санкт-Петербург

Leonid A. Shilenko, First-Year Resident, Laboratory Assistant

Department of Faculty Therapy with a Clinic; Laboratory of Pulmonary Vascular Disease

197341; Akkuratova str., 2;  Saint Petersburg

shilenko.leo@yandex.ruhttps://orcid.org/0000-0003-0114-5896КарповА. А.KarpovA. A.

Андрей Александрович Карпов, к.м.н., заведующий НИЛ, доцент, ведущий научный сотрудник

НИЛ патологии малого круга кровообращения; Институт медицинского образования; кафедра патологии; отдела «Технологии сильного искусственного интеллекта в физиологии и медицине»

Санкт-Петербург

Andrei A. Karpov, PhD, Head of Laboratory, Associate Professor, Leading Researcher

Laboratory of Pulmonary Vascular Disease; Department of Pathology; Department of “Strong Artificial Intelligence Technologies in Physiology and Medicine”

Saint Petersburg

karpov_aa@almazovcentre.ruhttps://orcid.org/0000-0002-8630-9847ВеретенниковаЕ. И.VeretennikovaE. I.

Елизавета Ивановна Веретенникова, клиническийординатор 2 года обучения

кафедра факультетской терапии им. профессора В. А. Вальдмана

Санкт-Петербург

Elizaveta I. Veretennikova, 2nd year Resident Physician

Department of Faculty Therapy named after Professor V. A. Valdman

Saint Petersburg

ШиленкоА. А.ShilenkoA. A.

Алексей Алексеевич Шиленко, лаборант-исследователь, инженер

НИЛ патологии малого круга кровообращения; факультет биотехнологий

Санкт-Петербург

Alexey A. Shilenko,  Laboratory Assistant

Laboratory of Pulmonary Vascular Disease

Saint Petersburg

lexa57575@gmail.comhttps://orcid.org/0000-0001-5129-9944ГалагудзаМ. М.GalagudzaM. M.

Михаил Михайлович Галагудза, д. м. н., профессор, член-корреспондент РАН, директор Института, заведующий кафедрой, ведущий научный сотрудник

Институт экспериментальной медицины; Институт медицинского образования; кафедра патологии; лаборатория радио- и оптоэлектронных приборов биоинформационных и геномных технологий ранней диагностики патологий живых систем

Санкт-Петербург

Michael M. Galagudza, MD, DSc, Director of Institute, Head of the Department; Professor, Corresponding Member of the Russian Academy of Science; Leading Researcher

Institute of Experimental Medicine; Department of Pathology;  Institute for Analytical Instrumentation; Laboratory of Radio and Optoelectronic Devices for Bioinformatics and Genomic Technologies for Early Diagnosis of Pathologies in Living Systems

Saint Petersburg

galagudza@almazovcentre.ruФедеральное государственное бюджетное учреждение «Национальный медицинский исследовательский центр имени В. А. Алмазова» Министерства здравоохранения Российской ФедерацииРоссияAlmazov National Medical Research CentreRussian FederationФедеральное государственное бюджетное учреждение «Национальный медицинский исследовательский центр имени В. А. Алмазова» Министерства здравоохранения Российской Федерации; Федеральное государственное автономное образовательное учреждение высшего образования «Санкт-Петербургский государственный электротехнический университет «ЛЭТИ» имени В. И. Ульянова (Ленина)»РоссияAlmazov National Medical Research Centre; Saint Petersburg Electrotechnical University “LETI”Russian FederationФедеральное государственное бюджетное образовательное учреждение высшего образования «Санкт-Петербургский государственный педиатрический медицинский университет» Министерства здравоохранения Российской ФедерацииРоссияSaint Petersburg State Pediatric Medical UniversityRussian FederationФедеральное государственное бюджетное учреждение «Национальный медицинский исследовательский центр имени В. А. Алмазова» Министерства здравоохранения Российской Федерации; Федеральное государственное бюджетное образовательное учреждение высшего профессионального образования «Санкт-Петербургский национальный исследовательский университет информационных технологий, механики и оптики»РоссияAlmazov National Medical Research Centre; University ITMORussian FederationФедеральное государственное бюджетное учреждение «Национальный медицинский исследовательский центр имени В. А. Алмазова» Министерства здравоохранения Российской Федерации; Федеральное государственное бюджетное учреждение науки «Институт аналитического приборостроения Российской академии наук»РоссияAlmazov National Medical Research Centre; Institute for Analytical Instrumentation of the Russian Academy of SciencesRussian Federation20241504202411187102Copyright © Шиленко Л.А., Карпов А.А., Веретенникова Е.И., Шиленко А.А., Галагудза М.М., 20242024Шиленко Л.А., Карпов А.А., Веретенникова Е.И., Шиленко А.А., Галагудза М.М.Shilenko L.A., Karpov A.A., Veretennikova E.I., Shilenko A.A., Galagudza M.M.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://transmed.almazovcentre.ru/jour/article/view/847

   Ишемический инсульт занимает одно из лидирующих мест среди всех причин инвалидизации и смертности. Ключевыми подходами к лечению этой патологии являются тромболитическая терапия и тромбоаспирация. Несмотря на доказанную эффективность, применение этих методов ограничено сравнительно узким терапевтическим окном. Учитывая это, сохраняется большая актуальность в дальнейшем изучении молекулярных механизмов ишемического-реперфузионного повреждения головного мозга в рамках концепции ишемического каскада. Воздействие на механизмы индукции и реализации различных видов программируемой клеточной гибели с помощью фармакологических агентов представляет собой перспективный подход к ослаблению повреждения головного мозга при ишемическом инсульте. В настоящем обзоре рассмотрены ключевые процессы, ведущие к необратимому повреждению нейронов и их гибели. Детально рассмотрены механизмы формирования и роль эксайтотоксичности, кальциевой перегрузки, оксидативного и нитрозильного стресса, дисфункции митохондрий, а также запуск сигнальных путей апоптоза и асептического воспаления. Обсужден вопрос различных вариантов клеточной гибели на фоне этих патологических процессов. Наряду с рассмотрением сигнальных путей, способствующих прогрессии повреждения головного мозга, отдельное внимание уделено активации при ишемии протективных сигнальных механизмов, обеспечивающих повышение резистентности клетки к гибели.

   Ischemic stroke is one of the leading causes of disability and mortality. The key approaches to the treatment of this pathology are thrombolytic therapy and thromboaspiration. Despite their proven efficacy, the application of these methods is limited by a relatively narrow therapeutic window. There remains a great relevance in the further study of the molecular mechanisms of ischemic- reperfusion brain damage within the framework of the ischemic cascade concept. The impact on the mechanisms of induction and implementation of various types of programmed cell death with the help of pharmacological agents is a promising approach to reduce brain damage in ischemic stroke. This review considers the key processes leading to irreversible damage to neurons and their death. The mechanisms of formation and the role of excitotoxicity, calcium overload, oxidative and nitrosyl stress, mitochondrial dysfunction, as well as the triggering of signaling pathways of apoptosis and aseptic inflammation are considered in detail. The issue of various variants of cell death against the background of these pathological processes is discussed. Along with the consideration of signaling pathways that contribute to the progression of brain damage, special attention is paid to the activation of protective signaling mechanisms during ischemia, which provide an increase in cell resistance to death.

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The authors declare that there are no conflicts of interest present.