Laboratory of Molecular Mechanisms of Neural Interactions

Epilepsy is a common neurological disease with serious consequences for the health and quality of life of patients. Pharmacoresistant epilepsy, diagnosed at an early age, significantly disrupts the normal development of a child and leads to significant cognitive and mental abnormalities, therefore, the study of the mechanisms of epilepsy development at an early age remains a priority task in the field of epileptology and neurobiology. One of the common causes of childhood epilepsy is cortical malformations, including focal cortical dysplasia (FCD). This study focuses on the experimental creation of FCD in rats by freezing a section of the cerebral cortex on the first day of their life and provoking febrile seizures (FS) on the 10th day of life. The novelty and uniqueness of this approach lies in the fact that it is precisely this complex two-impact effect on the developing brain that is highly likely to trigger the process of epileptogenesis. To better understand the mechanisms of epileptogenesis and the role of FCD in this process, we will compare a number of indicators in 4 groups of animals, namely in 1) control; 2) group with FCD; 3) group with FS; 4) group with FCD and FS. First, morphological changes occurring in the area of PCD will be analyzed, including changes in the ratio of neurons to glial cells, as well as various subtypes of excitatory and inhibitory neurons. Secondly, the effect of experimental PKD and FS on the expression level of synaptic receptors and other target genes involved in epileptogenesis will be studied: genes of pro-inflammatory cytokines IL-1b and TNF-α, glutamate transporters EAAT1 and EAAT2. Thirdly, we will study the electrophysiological features of neurons and changes in synaptic plasticity in in vitro models on slices obtained from the brains of model rats, and in vivo we will analyze convulsive readiness, register EEG and study changes in the behavior of these animals using cognitive tests. In addition, we will analyze the morphological features of brain tissue obtained during surgical operations in the treatment of children with pharmacoresistant epilepsy and compare them with those observed in experimental groups of animals. We believe that this study will help expand our knowledge of the pathophysiology of epilepsy and the effect of FCD on various aspects of brain activity and create fundamental prerequisites for the development of new treatment strategies for epilepsy.