According to the World Health Organization, about 5 million people die every year from cerebrovascular disease. At the same time, the proportion of cerebral infarction, or ischemic stroke (IS), among forms of acute cerebrovascular accident reaches 80-85%. Despite the active study of biochemical and morphological changes leading to acute cerebrovascular ischemia, the problem of early diagnosis, prevention, as well as predicting the outcome of this disease is still relevant. There is no doubt that the interruption of the ischemic cascade at earlier stages can be accompanied by a greater effect of treatment. A timely and effective pharmacological intervention requires a clear understanding of the pathochemical and biological processes underlying acute ischemia at the molecular level. High mortality and disability accompanying acute IS, dictate the need to create new diagnostic and prognosis algorithms both in the acute period of IS, and in the recovery period. According to some authors, elucidation of the pathways that underlie the pathogenetic mechanisms acting in the penumbra are of great clinical interest for the development of new diagnostic and therapeutic strategies. Studying the mechanisms of apoptosis and autophagy of neurons in the dynamics of the acute period of IS, modulation of the autophagy process in the penumbra zone can contribute to the development of new methods for the diagnosis and treatment of acute IS. The review presents the results of the latest experimental studies on the role of apoptosis and autophagy in the development of acute cerebral ischemia and attempts to modulate these processes in order to influence the ischemic cascade. The review was based on sources from such international and national data bases as Scopus, Web of Science, Springer, RINC.

The Fas/FasL system is known to play a central role in maintaining peripheral self-tolerance and tissue homeostasis of the organism [12, 18]. Fas-mediated apoptosis is induced by binding of the Fas(CD 95/APO-l/TNFRSF6)-receptor to the Fas(CD 95L/CD 178/TNFSF6)-ligand on the respective cells [24]. Triggering of the expression of cell surface Fas receptors (Fas) regulates the elimination of autoreactive T- and B-lymphocytes by apoptosis. It is known that impaired activation of Fas-mediated apoptosis in individual subpopulations of T-cells plays an important role in the pathogenesis of type 1 diabetes mellitus (T1DM). The main key point in the development of T1DM is resistance to apoptosis of activated autoreactive T-lymphocytes, which migrate from the bloodstream to the pancreas and take an active part in β-cells destruction. Аt the present time, most of the results on the study of Fas-mediated apoptosis in T1DM were obtained in experiments in vitro [11, 18, 31]. There is no doubt that in vivo autoimmune pathological changes are more profound, and extrapolation of the results obtained in the experiment to the organism is not always valid. Тhereby, it seems relevant to evaluate the efficiency of Fas-mediated apoptosis of T-lymphocytes in the blood of patients with T1DM, depending on the compensation phase and the duration of the disease. In the article, the markers of Fas-mediated apoptosis of peripheral blood lymphocytes in patients with type 1 diabetes mellitus and individuals with high risk of T1DM development have been studied. The surface expression of Fas in individual subpopulations of T-lymphocytes was еvaluated. The inhibition of Fas-mediated apoptosis of autoreactive CD 95+-cells by soluble Fas-receptor was detected in patients with decompensation of T1DM. In compensation phase of T1DM Fas-mediated apoptosis of lymphocyte was successfully realized via the soluble Fas ligand (sFasL). The increased level of soluble FasL was revealed in compensation phase of T1DM and in individuals with high risk of T1DM development. This probably has a protective value, since the soluble FasL is involved in the removal of the peripheral blood autoreactive CD 95+-cells.

Postischemic neuroinflammation is a critical pathophysiological process within the entire scheme of cerebral ischemia, covering early damage and the period of tissue repair. It is characterized by microglial and astroglial activation with increased expression of inflammatory mediators and is accompanied by impaired innate and adaptive immune responses. In acute ischemic stroke (IS), neuroinflammation is caused by the response of resident immune cells of microglia and peripheral immunocompetent cells infiltrating the brain tissue, which penetrate the blood-brain barrier (BBB) into the lesion. Recent studies have shown the important role of the NLRP3-mediated inflammation in the death of neurons and glial cells in acute IS. The review presents the main mechanisms of activation of NLRP3-mediated inflammation in acute IS, leading to the caspase-1 formation and the IL-1β and IL-18 release, which are involved in the initiation and progression of inflammation in the brain parenchyma. The literature data on the role of autophagy in the inhibition of postischemic neuroinflammation are summarized. Autophagy can suppress neuroinflammation through a wide range of the autophagy - related proteins. The role of autophagy as a negative regulator of NLRP3-mediated inflammation in acute IS is analyzed. Data on the participation of autophagic proteins Beclin-1, LC3, and p62 in the suppression of NLRP3 inflammation due to the induction of basic mitophagy are presented. Prospects for modulating autophagy aimed at suppressing postischemic neuroinflammation, including the inhibition of NLRP3-inflammasome, have been noted. The review was based on sources from international and national data bases: Scopus, Web of Science, Springer, RINC.

The purpose of this section of the monograph is to familiarize readers with the role of programmed cell death type 1—apoptosis in autoimmune destruction of the pancreas in type 1 diabetes mellitus (T1DM-1). The task of focusing the reader’s attention on the mechanisms of pancreatic b-cells apoptosis is explained by the fact that the interest of scientists in this problem continues to grow. Sections of the chapter are devoted to the modern concept of T1DM-1 immunopathogenesis, the role of insufficient apoptosis of circulating effector T cells, on the one hand, and enhanced apoptosis of b-cells, on the other hand. Special attention is paid to the prospects for the treatment and prevention of T1DM. The chapter presents the results of experimental studies on the role of apoptosis in the immunopathogenesis of T1DM. Separately, the results of the authors’ own studies are considered. The chapter was based on sources from international data bases: Scopus, Springer, PubMed. The authors express the hope that the chapter will contribute not only to a deeper understanding of the pathogenesis of T1DM, but also to arouse interest in the prospects for the treatment and prevention of this disease. The chapter is intended for students of medical universities and a wide range of readers with higher medical and biological education.

В течение последних десятилетий острый ишемический инсульт (ОИИ) является актуальной медицинской и социальной проблемой. Высокая смертность и инвалидизация, сопровождающие ОИИ, диктуют необходимость создания новых алгоритмов профилактики, диагностики и прогноза исхода заболевания. Помочь в этом могут надежные биологические маркеры и высокотехнологичные методы лабораторной диагностики. Результаты новейших исследований свидетельствуют о том, что апоптоз, аутофагия и некроз являются основными механизмами гибели нейронов при ОИИ. Тем не менее до конца не ясно, какой из этих процессов преобладает на конкретном этапе ишемического каскада и в большей степени влияет на исход заболевания. Исследования в области нейроиммунологии позволили установить сигнальные белки, инициирующие как апоптотическую, так и аутофагическую гибель клеток головного мозга при ОИИ. Эти белки действуют либо синергично за счет создания общих модулей, либо альтернативно, в качестве переключателей с одной клеточной программы на другую. По мнению ученых, исследование перекрестных взаимодействий между апоптозом и аутофагией и их отдельными медиаторами в патогенезе ОИИ представляет большой интерес. Сравнительная оценка динамики концентрации биомаркеров аутофагии и апоптоза в периферической крови пациентов с ОИИ в сопоставлении с динамикой тяжести неврологического дефицита и объемом поражения головного мозга поможет глубже понять перекрестные взаимодействия между этими процессами на разных этапах острого периода ишемического инсульта. По мнению ряда авторов, исследование белков, участвующих в индукции аутофагии и апоптоза при ОИИ, будет способствовать не только более глубокому пониманию патогенеза заболевания, но и созданию новых диагностических алгоритмов, разработке специфических биомаркеров, предикторов течения и исхода заболевания. Ключевые слова: апоптоз, аутофагия, острый ишемический инсульт, биомаркеры аутофагии, биомаркеры апоптоза, вестерн-блоттинг, проточная цитометрия.