Blood–Brain Barrier Dysfunction Leads to Pathological Potentiation of Excitatory Synaptic Transmission in the Hippocampus

Blood–brain barrier (BBB) dysfunction is associated with the development of neuronal hyperexcitability and epileptogenesis. The precise mechanisms by which BBB disruption affects synaptic transmission in the hippocampus remain under investigation. In the present study, we analyzed changes in excitatory synaptic transmission in the CA3-to-CA1 hippocampal network in vitro under conditions of experimentally induced BBB dysfunction. To mimic the early consequences of BBB breakdown, acute rat hippocampal slices were perfused with a modified artificial cerebrospinal fluid containing thrombin (5 U/mL). Spontaneous activity was recorded in the stratum radiatum of the CA1 region together with field excitatory postsynaptic potentials (fEPSP) evoked by stimulation of Schaffer collaterals. Application of a thrombin-containing solution of plasma ionic composition caused a rapid induction of seizure-like activity (SLA) in the CA1 region. Simultaneously, a pronounced and fast increase in fEPSP amplitude was observed. This enhancement reached a plateau within 10–15 min and remained stable throughout the recording period. Our results demonstrate that conditions simulating BBB dysfunction induce a pathological strengthening of excitatory synaptic transmission in hippocampal CA3-to-CA1 neuronal networks, manifested as a rapid and persistent increase in fEPSP amplitude and the development of SLA. The data obtained provide evidence for a direct link between BBB integrity loss and hippocampal hyperexcitability, which may contribute to the pathogenesis of neuronal hypersynchronization.