Changes in the expression of apoptosis-associated proteins in the temporal cortex and hippocampus of rats during long-term kindling and their correction with minolexin

Epilepsy is one of the most common and serious diseases of the brain, affecting more than 70 million people worldwide. Available anticonvulsants are able to suppress seizures in two thirds of patients, and in the remaining third of patients, epilepsy is considered drug-resistant and other types of treatment are required, such as surgery, which also does not always lead to positive results. Overcoming resistance is a complex task that requires an understanding of the biochemical pathways and general pathological processes underlying epilepsy, primarily apoptosis. The purpose of this work was to study the effect of the antibiotic minolexin on the levels of apoptosis and the expression of apoptosis-associated molecules (p53, Bcl-2, caspase-3 and caspase-8) in the temporal cortex, underlying white matter and hippocampus of Krushinsky-Molodkina rats with hereditary audiogenic epilepsy with long-term kindling. Materials and methods. We used Krushinsky-Molodkina rats at the age of 11 months, which were subjected to audiogenic stimulation and administered intraperitoneally with 1 ml of saline solution or the second-generation tetracycline series minolexin at a dose of 45 mg/kg, dissolved in saline solution for 14 days. The temporal lobe cortex and underlying white matter, the hippocampus, were examined. Apoptosis levels (TUNEL) and expression of apoptosis-associated proteins (p53, Bcl-2, caspase-3 and -8) were assessed (immunohistochemistry, Western blotting). Results. In Krushinsky-Molodkina rats with hereditary audiogenic epilepsy, an increase in the apoptosis level was shown during long-term kindling. A p53-mediated, but caspase-independent mechanism of apoptosis activation has been identified. When minolexin was administered, an anti-apoptotic and neuroprotective effect was observed in the temporal lobe and hippocampus of rats.