Abstract
Stroke is the leading cause of disability and death in the adult population. Modern methods of treating patients with acute ischemic stroke include thrombolytic therapy with a narrow therapeutic window and endovascular thrombectomy. The development of other methods of treatment of brain hypoxia in the penumbra zone is relevant. Mitochondria, which are involved in immediate and delayed molecular mechanisms of adaptation to hypoxic stress in the cerebral cortex, primarily respond to hypoxia. Hypoxia induces reprogramming of the mitochondrial respiratory chain function and switching from oxidation of substrates of the respiratory chain complex I to succinate oxidation (complex II). The brain's need for succinate increases. Clinical studies have shown a positive effect of drugs containing succinates on the course of stroke. The study of mitochondrial function is carried out mainly in an experiment. In the present study of mitochondrial disorders in stroke and chronic brain ischemia in adult patients, the quantitative method proposed by A. G. Pearse was used to assess the activity of mitochondrial enzymes of peripheral blood lymphocytes, which are referred to as the enematic mirror of tissues. In acute cerebral ischemia, a compensatory increase in the activity of succinate dehydrogenase was observed on the first day, indicating the tension (increased activity) of the second complex of the mitochondrial respiratory chain.. These data confirm the need to prescribe succinic acid in the acute phase of stroke. At the same time, the dose of 250 mg per day is not sufficient for patients with increased body weight. The standard dose of the drug should be higher, taking into account the different body weight of patients. In patients with stroke, there was also a decrease in the activity of α-glycerophosphate dehydrogenase, which is involved in the fat metabolism of mitochondria, which is an indication for the appointment of carnitine. In chronic brain ischemia, the activity of succinate dehydrogenase and α-glycerophosphate dehydrogenase decreased, indicating indications for the appointment of idebenone and carnitine along with vasodilator therapy and endovascular thrombectomy. Thus, the results of a study of mitochondrial function in patients with acute and chronic brain ischemia are presented. Violations of complex II in the respiratory chain cycle and violation of fat metabolism were revealed, indicating indications for the appointment of energotropic therapy.
Highlights
Stroke is the leading cause of disability and death in the adult population
Reversible, compensatory activation of the respiratory chain complex II is the main mechanism of direct adaptation to hypoxia, which is necessary for (1) succinate-bound energy synthesis in conditions of oxygen deficiency and the formation of urgent resistance in the body; (2) succinaterelated stabilization of HIF-1A and initiation of its transcriptional activity associated with the formation of longterm adaptation; (3) succinate-related activation of the GPR91 succinate-specific receptor [2,3,4,5]
The purpose of this study is to study mitochondrial disorders in the pathogenesis of acute and chronic brain ischemia in patients to improve the effectiveness of care for this pathology
Summary
Stroke is the leading cause of disability and death in the adult population. Modern advanced treatment methods for patients with acute ischemic stroke include thrombolytic therapy and endovascular thrombectomy. It is known that mitochondria – cellular organelles that are the energy stations of the cell-primarily react to hypoxia This cellular bioenergetic apparatus is involved in the development of immediate and delayed molecular mechanisms of adaptation to hypoxic stress in the cerebral cortex. Hypoxic expression of GPR91 is tissue-specific and depends on the duration and severity of hypoxia It is maximal in the cerebral cortex. Hypoxia-induced direct expression of HIF-1A transcription factor in the cerebral cortex is regulated by succinate and induced by medicines containing succinate [3]. These data indicate an increased need of the brain for succinate in hypoxia. Clinical studies have shown a positive effect of drugs containing succinates on the course of stroke [6,7,8,9,10,11]
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