Blood-brain barrier disfunction and development of epileptic seizures (according to the materials of scientific report at the meeting of the Presidium of NAS of Ukraine, December 23, 2020)

Abstract

Blood-brain barrier dysfunction (BBB) is an important factor to the development of epilepsy and its behavioral comorbidities. Disruption of its integrity is accompanied by the ingress of blood components, including thrombin, into the cerebrospinal fluid. The effect of thrombin is mediated mainly through its major receptor, protease-activated receptors 1 (PAR1). Using lithium-pilocarpine model of seizures, we show that downregulation of PAR1 activity reduces anxiety and aggressive behavior in epileptic rats and restores distinct forms of hippocampal synaptic plasticity in experimental model of temporal-lobe epilepsy. Taken together, our data suggest that PAR1-signaling promotes the development of acquired epilepsy. PAR1 may be a new potential target for the treatment of this disorder and associated behavioral pathologies.