Церебропротекторное действие нового аналога халкона при экспериментальной черепно-мозговой травме. Фокус на митохондриальный биогенез и нейровоспаление

Abstract

INTRODUCTION: Currently, the treatment of traumatic brain injuries requires a comprehensive approach which includes, among other things, the use of drugs possessing cerebroprotective activity. As a rule, the action of cerebral protectors is concentrated on separate pathophysiological mechanisms of brain damage, for example, the mitochondrial dysfunction. AIM: To study the effect of a new chalcone analogue on changes in the processes of mitochondrial biogenesis and neuroinflammation in rats with experimental traumatic brain injury. MATERIALS AND METHODS: In the work, rats of Wistar line were used in whom a traumatic brain injury was modeled by a single exposure of the parietal region of the skull to a freely falling weight. The studied compound and the comparison drug, choline alfoscerate, were introduced orally within 7 days after injury, at doses of 50 mg/kg and 150 mg/kg, respectively. The behavioral reactions of the animals were evaluated in the ‘open field’ test. The intensity of neuroinflammation was determined by changes in the concentrations of IL-1β, IL-6 and TNF-α in the brain tissue. The markers of mitochondrial biogenesis were changes in the activity of succinate dehydrogenase and cytochrome c oxidase. RESULTS: In the course of the work, it was found that the use of a new chalcone analogue in conditions of experimental traumatic brain injury facilitates an increase in locomotor and exploratory activity in rats, as well as reduces the level of anxiety. With the introduction of the studied compound, a decrease in the intensity of neuroinflammation reactions was observed, as evidenced by a decrease in the content of IL-1β by 58.8% (p < 0.05), IL-6 by 55.0% (p < 0.05) and TNF-α by 50.7% (p < 0.05) compared with untreated animals. The activity of succinate dehydrogenase and cytochrome c oxidase increased by 63.6% (p < 0.05) and 27.6% (p < 0.05), respectively, when using the studied chalcone analogue. To note, the activity of enzymatic markers of mitochondrial biogenesis in rats treated with chalcone analogue was higher than in animals who were introduced choline alfoscerate. CONCLUSIONS: The study showed for prospects of further investigation of a new chalcone analogues as a complex cerebroprotective agent for treatment of sequelae of a traumatic brain injury.