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Brivaracetam Prevents the Over-expression of Synaptic Vesicle Protein 2A and Rescues the Deficits of Hippocampal Long-term Potentiation In Vivo in Chronic Temporal Lobe Epilepsy Rats

[ Vol. 17 , Issue. 4 ]

Author(s):

Yu-Xing Ge, Ying-Ying Lin, Qian-Qian Bi and Yu-Juan Chen*   Pages 354 - 360 ( 7 )

Abstract:


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 calcium channels.

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.

Keywords:

Temporal lobe epilepsy, synaptic vesicle protein 2A, brivaracetam, synaptic plasticity, long-term potentiation, cognitive deficits.

Affiliation:

Department of Neurology, Tongji University Affiliated Tenth People's Hospital, 200072 Shanghai, Department of Neurology, Tongji University Affiliated Tenth People's Hospital, 200072 Shanghai, Department of Neurology, Tongji University Affiliated Tenth People's Hospital, 200072 Shanghai, Department of Neurology, Tongji University Affiliated Tenth People's Hospital, 200072 Shanghai



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