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Information × Registration Number 0219U102053, 0119U102351 , R & D reports Title Mechanisms of epileptiform activity and properties of hippocampal synaptic plasticity due to dysfunction of the blood-brain barrier popup.stage_title Head Savotchenko Alina V., Registration Date 16-12-2019 Organization Bogomolets Institute of Physiology popup.description2  Recent studies suggest that BBB dysfunction is an important contributor to epilepsy and concomitant psychoneurological disorders. Our recent studies have shown that the concentration of serine protease, thrombin, increases significantly in brain tissue after experimentally induced status epilepticus (SE). Moreover, thrombin acting through its major receptor, protease-activated receptor 1 (PAR1), contributes to neuronal damage and EC-induced epileptogenesis. Because thrombin and PAR1 are involved in synaptic plasticity and memory formation, the purpose of this stage of the study was to investigate the involvement of PAR1 in synaptic plasticity and post-SE behavioral deficits. Using the lithium-pilocarpine model of SE, we showed that the downregulation of PAR1 activity shortly after the end of SE attenuates anxiolytic behavior in experimental animals two weeks after SE. Inhibition of PAR1 restores clear forms of synaptic hippocampal plasticity in a trial-generalized experimental model. Taken together, our data highlight the important role of PAR1 in EC-induced synaptic and behavioral changes and provide new insights into the cellular mechanisms underlying epilepsy-related behavioral disorders. We also conducted an experimental study of the effect of a selective PAR1 antagonist on the excitatory behavior of rats with SE. In previous work, we have shown that PAR1 inhibition exhibits neuroprotective properties in the CA1 area of the hippocampus, decreases the number and duration of recurrent unprovoked seizures, and reduces the mortality of rats. The experimental data obtained in this work indicate that blocking of PAR1 leads to normalization of emotional excitability of rats in the latent stage of formation of temporal epilepsy in the lithium-pilocarpine model of status epilepticus. In this work, we first demonstrated the effect of blocking PAR1 on emotional excitability in the early stages of epilepsy formation. Product Description popup.authors Semenikhina Margaryta O. Shypshyna Mariia S. popup.nrat_date 2020-04-02 Close