Abstract
The aim of the study was to reveal the influence of the JNK inhibitor on the induction of disturbances in the psychoneurological status of experimental animals in the modeling of posthypoxic encephalopathy and to reveal the mechanisms of its action related to the functioning of the neural stem cells of the brain. Materials and methods. The experiments were performed on 64 male outbred mice. Posthypoxic encephalopathy was modeled in non-native mice with hypoxia of the hermetic volume. The JNK inhibitor was administered to mice subcutaneously at a dose of 15 mg/kg once before hypoxic exposure. We studied the neuropsychiatric status, the content of neuronal stem cells in the subventricular zone of the brain of experimental animals, and the direct effect of the JNK inhibitor on intact neural stem cells in vitro. Results. The expressed cerebroprotective action of the pharmacological agent was revealed, which consisted of normalizing the indices of orientation and exploratory behavior and conditioned activity in experimental animals. These effects developed against a background of a significant increase in the content of neural stem cells in the subventricular zone of the brain. In the experiments in vitro, a direct stimulating effect of the JNK inhibitor on neural stem cells was found. Conclusions. The obtained results showed a neuroprotective action of the JNK inhibitor. At the same time, the prevention and compensation of the development of disturbances in the activity of the central nervous system is based on the preservation of the ability of the nerve tissue to repair andassociated with the functioning of resident neural stem cells.
Highlights
The expressed cerebroprotective action of the pharmacological agent was revealed, which consisted of normalizing the indices of orientation and exploratory behavior and conditioned activity in experimental animals
These effects developed against a background of a significant increase in the content of neural stem cells in the subventricular zone of the brain
The obtained results showed a neuroprotective action of the Jun N-terminal kinase (JNK) inhibitor
Summary
Нейропротективные свойства ингибитора C-Jun N-terminal kinase (JNK) при гипоксической гипоксии. Гольдберга, Томский национальный исследовательский медицинский центр (НИМЦ) Российской академии наук Россия, 634028, г. Цель исследования – выявить влияние ингибитора JNK на формирование нарушений психоневрологического статуса экспериментальных животных при моделировании постгипоксической энцефалопатии и вскрыть механизмы его действия, связанные с функционированием нейральных стволовых клеток (СК) головного мозга. Содержание нейральных СК в субвентрикулярной зоне головного мозга экспериментальных животных и прямое влияние ингибитора JNK на интактные нейральные СК в условиях in vitro. При этом в экспериментах in vitro обнаружено прямое стимулирующее влияние ингибитора JNK на нейральные СК. Полученные результаты свидетельствуют о выраженном нейропротекторном действии ингибитора JNK. Ключевые слова: регенеративная медицина, церебропротекторные средства, ингибитор JNK, сигнальная трансдукция, энцефалопатия, нейральные стволовые клетки. Авторы декларируют отсутствие явных и потенциальных конфликтов интересов, связанных с публикацией настоящей статьи.
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