Extracellular bromide enhances GABAA receptor function in the immature, but not the adolescent rat pilocarpine epilepsy model

IF 2 4区医学 Q3 CLINICAL NEUROLOGY

Epilepsy Research Pub Date : 2025-03-01 DOI:10.1016/j.eplepsyres.2025.107535

Heiner Kolp , Jana K. Hackert , Marco Heerdegen , Christa Unger , Tina Sellmann , Katrin Porath , Valentin Neubert , Marco Weiergräber , Timo Kirschstein , Rüdiger Köhling

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引用次数: 0

Abstract

Objective

To study the effects of extracellular bromide in a novel immature rat pilocarpine model compared to the standard adolescent rat model.

Methods

We employed an immature rat model of repetitive pilocarpine-induced status epilepticus (340 mg/kg on postnatal days 9, 11 and 15). The electrophysiological characterization of the Schaffer collateral CA1-synapse and of CA1 pyramidal neurons was performed in 30–70 day-old animals. To explore the effects of bromide, 20 mM NaCl in the bath solution was replaced by 20 mM NaBr. We compared our findings in the immature model with data from the standard adolescent model of a single pilocarpine-induced status epilepticus (340 mg/kg on postnatal day 30) obtained from 40−90 day-old animals.

Results

In the immature, but not in the adolescent model, extracellular bromide (20 mM) enhanced the GABA_A-receptor component of the inhibitory postsynaptic potential, hyperpolarized the GABA_A-receptor reversal potential and reduced intrinsic excitability. However, bromide left high-frequency stimulation-induced long-term potentiation unaltered – in both the immature and the adolescent model.

Significance

The immature model, but not the commonly used adolescent pilocarpine model, showed a persistent bromide-enhanced GABA_A-receptor function leading to reduced intrinsic excitability. Hence, we suggest that immature animal models are needed to explore novel therapeutic strategies for epilepsies acquired during infancy.

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方法我们采用了一种未成熟大鼠皮洛卡品诱导的重复性癫痫状态模型（340 mg/kg，出生后第 9、11 和 15 天）。对出生后 30-70 天的大鼠进行了沙弗侧索 CA1 突触和 CA1 锥体神经元的电生理特征描述。为了探究溴化物的影响，我们将浴液中的 20 mM NaCl 替换为 20 mM NaBr。我们将未成熟模型的研究结果与标准青少年模型的数据进行了比较，标准青少年模型是在出生后第 30 天用皮洛卡品诱发癫痫状态（340 毫克/千克），这些数据来自出生后 40-90 天的动物。结果在未成熟模型中，细胞外溴化物（20 mM）增强了抑制性突触后电位的 GABAA 受体成分，使 GABAA 受体反转电位超极化，并降低了内在兴奋性。然而，无论是在未成熟模型还是在青少年模型中，溴化物都不会改变高频刺激诱导的长期电位。重要意义未成熟模型显示出持续的溴化物增强 GABAA 受体功能，导致内在兴奋性降低，而常用的青少年皮洛卡品模型则没有。因此，我们建议需要未成熟动物模型来探索婴儿期癫痫的新型治疗策略。

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.