Effect of trans 4-butylcyclohexane carboxylic acid (4-BCCA) upon neurodegeneration, oxidative stress related to epileptogenesis in pilocarpine-induced status epilepticus

IF 2 4区医学 Q3 CLINICAL NEUROLOGY

Epilepsy Research Pub Date : 2024-11-08 DOI:10.1016/j.eplepsyres.2024.107471

Deeksha Sharma , Sudhir Chandra Sarangi , Surabhi Sinha , Soumya Sucharita Pattnaik , Yajnaseni Dash , Aruna Nambirajan , Tapas Chandra Nag , Surender Singh , Matthew C. Walker

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引用次数: 0

Abstract

Objective

4-butylcyclohexane carboxylic acid (4-BCCA), a low-affinity inhibitor of AMPA receptors at the trans-membrane domain have been suggested as potential therapeutic option for epilepsy, but its potential impact on status epilepticus and disease-modification and neurodegeneration following status epilepticus have not been investigated.

Methods

This study established the effect of 4-BCCA along with standard antiseizure medications (ASMs) [valproate (VPA) and perampanel (PER)] in Li-pilocarpine induced status epilepticus rat model. We first established the effective dose of 4-BCCA in status epilepticus followed by an acute and long-term effect study. Assessments of neurobehaviour (by elevated plus maze and passive avoidance), neurodegeneration [by transmission electron microscopy (TEM) and immunohistochemistry in hippocampal slices], total antioxidant capacity (TAC) and neuronal loss [by neuron specific enolase (NSE) in cerebral tissue] were performed.

Results

4-BCCA at 200 mg/kg. i.p. was found to be an effective dose and in comparison, to other ASMs it showed better seizure control in terms of latency and number of stage 3/4 seizures. PER group and 4-BCCA+PER showed better memory retention but without significant difference among the drug-treated groups. In TEM, 4-BCCA+PER and 4-BCCA+VPA group showed less nucleus and cytoplasmic changes. In immunohistochemistry 4-BCCA, PER and combination groups showed better neuronal viability. 4-BCCA+ PER showed higher TAC and lower NSE level.

Significance

4-BCCA alone and its combination with ASMs especially perampanel in status epilepticus model in rats showed better seizure control and neuroprotection.

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反式 4-丁基环己烷羧酸（4-BCCA）对皮质类药物诱发的癫痫状态中与癫痫发生相关的神经变性和氧化应激的影响

目的4-丁基环己烷羧酸（4-BCCA）是一种跨膜结构域的 AMPA 受体低亲和力抑制剂，已被认为是治疗癫痫的潜在选择，但其对癫痫状态、疾病修饰和癫痫状态后神经变性的潜在影响尚未得到研究。方法本研究确定了 4-BCCA 与标准抗癫痫药物（ASMs）[丙戊酸钠（VPA）和过潘奈尔（PER）]在利血平诱导的状态性癫痫大鼠模型中的作用。我们首先确定了 4-BCCA 对癫痫状态的有效剂量，然后进行了急性和长期效应研究。我们对大鼠的神经行为（通过高架迷宫和被动回避）、神经变性（通过海马切片的透射电子显微镜（TEM）和免疫组化）、总抗氧化能力（TAC）和神经元损失（通过脑组织中的神经元特异性烯醇化酶（NSE））进行了评估。结果发现，4-BCCA（200 毫克/千克，静脉注射）是一种有效剂量，与其他 ASM 相比，它在潜伏期和 3/4 期癫痫发作次数方面显示出更好的癫痫发作控制效果。PER 组和 4-BCCA+PER 显示出更好的记忆保持能力，但各药物治疗组之间没有显著差异。在 TEM 中，4-BCCA+PER 组和 4-BCCA+VPA 组的细胞核和细胞质变化较少。在免疫组化中，4-BCCA、PER 和联合组显示出更好的神经元活力。意义4-BCCA单药及其与ASMs（尤其是perampanel）的联合用药在大鼠癫痫状态模型中显示出更好的癫痫控制和神经保护作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Epilepsy Research 医学-临床神经学

CiteScore

0.10

自引率

4.50%

发文量

143

审稿时长

62 days

期刊介绍： Epilepsy Research provides for publication of high quality articles in both basic and clinical epilepsy research, with a special emphasis on translational research that ultimately relates to epilepsy as a human condition. The journal is intended to provide a forum for reporting the best and most rigorous epilepsy research from all disciplines ranging from biophysics and molecular biology to epidemiological and psychosocial research. As such the journal will publish original papers relevant to epilepsy from any scientific discipline and also studies of a multidisciplinary nature. Clinical and experimental research papers adopting fresh conceptual approaches to the study of epilepsy and its treatment are encouraged. The overriding criteria for publication are novelty, significant clinical or experimental relevance, and interest to a multidisciplinary audience in the broad arena of epilepsy. Review articles focused on any topic of epilepsy research will also be considered, but only if they present an exceptionally clear synthesis of current knowledge and future directions of a research area, based on a critical assessment of the available data or on hypotheses that are likely to stimulate more critical thinking and further advances in an area of epilepsy research.