Molecular mechanisms of neuroprotection of 3-[(E)-3-(3,5-ditret-butyl-4-hydroxyphenyl)-3-oxoprop-1-enyl]-6-methoxy-chromene-4-one in experimental traumatic brain injury

Introduction. Neuroprotection in traumatic brain injury is a promising area of therapy for cerebral disorders. Neuroprotective effect can be implemented by a action on variety molecular targets, a change in the activity of which leads to the elimination of pathogenetic reactions of secondary brain damage. Such targets can include the ultrastructures of the mitochondria of the cell. The aim of the study. To evaluate possible molecular mechanisms of neuroprotection of 3-[(E)-3-(3,5-ditret-butyl-4-hydroxyphenyl)-3-oxoprop-1-enyl]-6-methoxy-chromene-4-one in the context of changes in mitochondrial function under experimental traumatic brain injury. Material and methods. Traumatic brain injury was simulated in Wistar rats by free-falling of a load (150 g) from a height of 50 cm onto the parietal region of the animal's skull. The tested compound and the reference medication (ethylmethylhydroxypyridine succinate) were administered per os for 7 days after injury. After the specified time, the degree of development of neurological deficiency in animals was determined on the mNSSscale, the activity of enzymes in brain tissue was evaluated: succinate dehydrogenase, citrate synthase, cytochrome c oxidase and aconitase. The change in the concentration of annexin Vwas also evaluated. Results. It was found that the use of the tested compound and the reference significantly reduced the severity of neurological symptoms in rats by 31.6% (p<0.05) and 43.4% (p<0.05), respectively, relative to untreated animals. At the same time, the adminiatrstion of 3-[(E)-3-(3,5-ditret-butyl-4-hydroxyphenyl)-3-oxoprop-1-enyl]-6-methoxy-chromene-4-one led to a more pronounced increase in the activity of the evaluated enzymes than the use of the referent. The concentration of annexin V decreased against the background of the administration of the tested compound and the reference by 18.7% (p <0.05) and 31.8% (p <0.05), respectively, by animals. Conclusion. The study showed that the administration of 3-[(E)-3-(3,5-ditret-butyl-4-hydroxyphenyl)-3-oxoprop-1-enyl]-6-methoxy-chromene-4-one to animals under experimental traumatic brain injury increases the activity of enzymes of cellular metabolism: succinate dehydrogenase, citrate synthase, cytochrome c oxidase and aconitase, which in turn can lead to reduction of apoptosis reactions and development of neuroprotective effect.