Demonstration of the effect of brivaracetam on an experimental epilepsy model

Mustafa Çeti̇ner,Hasan Emre Aydin

doi:10.3906/sag-1806-236

Abstract

The aim of this study was to investigate the effects of valproic acid (VPA) and a new-generation antiepileptic drug called brivaracetam (BRV) on the brain damage occurring after status epilepticus (SE) in rats. In our study, an experimental animal model of SE, generated by stereotaxically injecting 0.4–2 μg of kainic acid into the rat hippocampus, was used. The laboratory animals were divided into 4 groups: the first group was a sham group that was subjected to anesthesia and SE was not induced; the second group was a SE group, in which SE was induced using kainic acid but subjects were not treated; the third group was the VPA group, in which SE was induced using kainic acid and subjects were treated with VPA; and the fourth group was the BRV group, in which SE was induced using kainic acid and subjects were treated with BRV. Annexin V and p53 levels were statistically higher in the SE group than in the sham group (P < 0.001). Following the treatment with VPA and BRV, a substantial decrease was observed in the annexin V and p53 levels compared to those of the SE group (P < 0.001). There was a statistically significant increase in Bcl-2 levels after VPA and BRV treatment compared to the SE group (P < 0.001). Our study showed that VPA and BRV are protective against neuronal damage occurring after SE in rats due to the increase in Bcl-2.

Highlights

Status epilepticus (SE) is a medical emergency with significant mortality, in which the seizure lasts continuously for more than 5 min and causes severe neuronal cell death [1]
Our study showed that valproic acid (VPA) and BRV are protective against neuronal damage occurring after SE in rats due to the increase in Bcl-2
The activated p53 ensures it by increasing the expression of Bax and Bak from two proapoptotic Bcl-2 family proteins [10]. p53depleted mouse neurons are resistant to apoptosis induced by seizure and/or excitotoxins [11]

Summary

Introduction

Status epilepticus (SE) is a medical emergency with significant mortality, in which the seizure lasts continuously for more than 5 min and causes severe neuronal cell death [1]. Experimental and clinical studies have shown that prolonged seizures can cause neuronal death in the brain [3,4,5]. Antiapoptotic proteins are the Bcl-2 gene family proteins, which are important regulators of the apoptosis process. The proteins belonging to the Bcl-2 family are the main regulators of the cell death signals targeting the mitochondria and contribute to seizure-induced neuronal death [9]. The activated p53 ensures it by increasing the expression of Bax and Bak from two proapoptotic Bcl-2 family proteins [10]. The activated p53 ensures it by increasing the expression of Bax and Bak from two proapoptotic Bcl-2 family proteins [10]. p53depleted mouse neurons are resistant to apoptosis induced by seizure and/or excitotoxins [11]

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