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匹鲁卡品在大鼠中诱导剂量依赖性差异癫痫表型:转化潜力的考虑。

Dose-Dependent Induction of Differential Seizure Phenotypes by Pilocarpine in Rats: Considerations for Translational Potential.

机构信息

Clinical Centre of Serbia, University Eye Hospital, Pasterova 2, 11000 Belgrade, Serbia.

Institute of Medical Physiology "Richard Burian", Faculty of Medicine, University of Belgrade, Višegradska 26/II, 11000 Belgrade, Serbia.

出版信息

Medicina (Kaunas). 2024 Sep 26;60(10):1579. doi: 10.3390/medicina60101579.

Abstract

: Pilocarpine is used in experimental studies for testing antiepileptic drugs, but further characterization of this model is essential for its usage in testing novel drugs. The aim of our study was to study the behavioral and EEG characteristics of acute seizures caused by different doses of pilocarpine in rats. : Male Wistar rats were treated with a single intraperitoneal dose of 100 mg/kg (P100), 200 mg/kg (P200), or 300 mg/kg (P300) of pilocarpine, and epileptiform behavior and EEG changes followed within 4 h. : The intensity and the duration of seizures were significantly higher in P300 vs. the P200 and P100 groups, with status epilepticus dominating in P300 and self-limiting tonic-clonic seizures in the P200 group. The seizure grade was significantly higher in P200 vs. the P100 group only during the first hour after pilocarpine application. The latency of seizures was significantly shorter in P300 and P200 compared with P100 group. : Pilocarpine (200 mg/kg) can be used as a suitable model for the initial screening of potential anti-seizure medications, while at a dose of 300 mg/kg, it can be used for study of the mechanisms of epileptogenesis.

摘要

匹鲁卡品用于实验研究以测试抗癫痫药物,但为了在测试新药物中使用该模型,进一步对其特征进行描述是必不可少的。我们的研究目的是研究不同剂量匹鲁卡品诱发的急性大鼠癫痫发作的行为和脑电图特征。

雄性 Wistar 大鼠腹腔内单次给予 100mg/kg(P100)、200mg/kg(P200)或 300mg/kg(P300)的匹鲁卡品,在 4 小时内观察癫痫样行为和脑电图变化。

P300 组的癫痫发作强度和持续时间明显高于 P200 和 P100 组,癫痫持续状态在 P300 组占主导地位,自限性强直-阵挛性发作在 P200 组占主导地位。与 P100 组相比,P200 组在匹鲁卡品应用后 1 小时内的癫痫发作分级显著升高。与 P100 组相比,P300 和 P200 组的癫痫发作潜伏期明显缩短。

匹鲁卡品(200mg/kg)可作为潜在抗癫痫药物初步筛选的合适模型,而在 300mg/kg 剂量下,可用于研究癫痫发生的机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3996/11509679/5056e4946ae1/medicina-60-01579-g001.jpg

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