Abstract：
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.
The aim of this study was to explore the neuroprotective mechanism of BRV on synaptic plasticity in experimental TLE rats.
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.
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.
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.
The aim of this study was to explore the neuroprotective mechanism of BRV on synaptic plasticity in experimental TLE rats.
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.
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.
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.
摘要：
颞叶癫痫（TLE）患者通常患有认知障碍和反复发作。布立西坦（BRV）是一种新型的抗癫痫药物（AEDs），最近用于治疗有或没有继发性推广的部分性癫痫发作。与其他AED不同，BRV在突触可塑性方面具有一些有利的性质。然而,潜在的机制仍然难以捉摸。
本研究旨在探讨BRV对实验性TLE大鼠突触可塑性的神经保护机制。
通过体内场兴奋性突触后电位（fEPSP）的测量，在毛果芸香碱诱导的TLE模型上评估了BRV（10mg/kg）慢性治疗的效果。用免疫印迹法鉴定了差异表达的突触囊泡蛋白2A（SV2A）。然后，在TLE模型中长时程增强(LTP)诱导过程中,突触体相关蛋白25(SNAP-25)的快速磷酸化研究了BRV对突触可塑性的潜在作用.
在癫痫大鼠中显示出海马中SV2A水平的升高伴随着LTP的降低。此外，BRV治疗持续30天以上，改善了癫痫大鼠SV2A的过表达，逆转了突触功能障碍。此外,BRV治疗减轻了癫痫患者LTP诱导过程中Ser187上SNAP-25的异常磷酸化，这与突触小泡胞吐和电压门控钙通道的调节有关。
BRV治疗改善了癫痫大鼠海马中SV2A的过度表达并挽救了突触功能障碍。这些结果确定了BRV对TLE模型的神经保护作用。
本研究旨在探讨BRV对实验性TLE大鼠突触可塑性的神经保护机制。
通过体内场兴奋性突触后电位（fEPSP）的测量，在毛果芸香碱诱导的TLE模型上评估了BRV（10mg/kg）慢性治疗的效果。用免疫印迹法鉴定了差异表达的突触囊泡蛋白2A（SV2A）。然后，在TLE模型中长时程增强(LTP)诱导过程中,突触体相关蛋白25(SNAP-25)的快速磷酸化研究了BRV对突触可塑性的潜在作用.
在癫痫大鼠中显示出海马中SV2A水平的升高伴随着LTP的降低。此外，BRV治疗持续30天以上，改善了癫痫大鼠SV2A的过表达，逆转了突触功能障碍。此外,BRV治疗减轻了癫痫患者LTP诱导过程中Ser187上SNAP-25的异常磷酸化，这与突触小泡胞吐和电压门控钙通道的调节有关。
BRV治疗改善了癫痫大鼠海马中SV2A的过度表达并挽救了突触功能障碍。这些结果确定了BRV对TLE模型的神经保护作用。
