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 ofthe brain, affecting more than 70 million people worldwide. Availableanticonvulsants are able to suppress seizures in two thirds of patients,and in the remaining third of patients, epilepsy is considered drug-resistantand other types of treatment are required, such as surgery, whichalso does not always lead to positive results. Overcoming resistanceis a complex task that requires an understanding of the biochemicalpathways and general pathological processes underlying epilepsy,primarily apoptosis. The purpose of this work was to study the effectof the antibiotic minolexin on the levels of apoptosis and the expressionof apoptosis-associated molecules (p53, Bcl-2, caspase-3 and caspase-8)in the temporal cortex, underlying white matter and hippocampus ofKrushinsky–Molodkina rats with hereditary audiogenic epilepsy withlong-term kindling. We used Krushinsky–Molodkina rats at the ageof 11 months, which were subjected to audiogenic stimulation andadministered intraperitoneally with 1 mL of saline solution or thesecond-generation tetracycline series minolexin at a dose of 45mg/kg, dissolved in saline solution for 14 days. The temporal lobecortex and underlying white matter, the hippocampus, were examined.Apoptosis levels (TUNEL) and expression of apoptosis-associatedproteins (p53, Bcl-2, caspase-3 and -8) were assessed (immunohistochemistry,Western blotting). In Krushinsky–Molodkina rats with hereditaryaudiogenic epilepsy, an increase in the apoptosis level was shownduring long-term kindling. A p53-mediated, but caspase-independentmechanism of apoptosis activation has been identified. When minolexinwas administered, an anti-apoptotic and neuroprotective effect wasobserved in the temporal lobe and hippocampus of rats.