Background: Patients with temporal lobe epilepsy (TLE) usually suffer from cognitive
deficits and recurrent seizures. Brivaracetam (BRV) is a novel anti-epileptic drug (AEDs) recently
used for the treatment of partial seizures with or without secondary generalization. Different from
other AEDs, BRV has some favorable properties on synaptic plasticity. However, the underlying
mechanisms remain elusive.
Objective: The aim of this study was to explore the neuroprotective mechanism of BRV on synaptic
plasticity in experimental TLE rats.
Methods: The effect of chronic treatment with BRV (10 mg/kg) was assessed on Pilocarpine induced
TLE model through measurement of the field excitatory postsynaptic potentials (fEPSPs) in
vivo. Differentially expressed synaptic vesicle protein 2A (SV2A) were identified with immunoblot.
Then, fast phosphorylation of synaptosomal-associated protein 25 (SNAP-25) during
long-term potentiation (LTP) induction was performed to investigate the potential roles of BRV on
synaptic plasticity in the TLE model.
Results: An increased level of SV2A accompanied by a depressed LTP in the hippocampus was
shown in epileptic rats. Furthermore, BRV treatment continued for more than 30 days improved
the over-expression of SV2A and reversed the synaptic dysfunction in epileptic rats. Additionally,
BRV treatment alleviates the abnormal SNAP-25 phosphorylation at Ser187 during LTP induction
in epileptic ones, which is relevant to the modulation of synaptic vesicles exocytosis and voltagegated
Conclusion: BRV treatment ameliorated the over-expression of SV2A in the hippocampus and
rescued the synaptic dysfunction in epileptic rats. These results identify the neuroprotective effect
of BRV on TLE model.