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匹鲁卡品诱导的大鼠癫痫发生:癫痫持续状态初始持续时间对电生理和神经病理学改变的影响

Pilocarpine-induced epileptogenesis in the rat: impact of initial duration of status epilepticus on electrophysiological and neuropathological alterations.

作者信息

Klitgaard Henrik, Matagne Alain, Vanneste-Goemaere Jocelyne, Margineanu Doru-Georg

机构信息

Preclinical CNS Research, UCB SA Pharma Sector, Chemin du Foriest, B-1420 Braine-l'Alleud, Belgium.

出版信息

Epilepsy Res. 2002 Sep;51(1-2):93-107. doi: 10.1016/s0920-1211(02)00099-2.

Abstract

This study characterized the electrophysiological and neuropathological changes in rat brains caused by pilocarpine (PILO)-induced status epilepticus (SE) of different duration. SE induced by PILO (375 mg/kg, i.p. adm.) were terminated with a bolus dose of diazepam (10 mg/kg, i.v. adm.) injected 7.5, 15, 30, 60 or 120 min after initiation of the secondary generalization of the SE. Three weeks later, the gain in body weight was significantly reduced in the rats exposed to PILO-induced SE lasting 30 min or more, when compared to controls. Spontaneous seizures were not detected in rats with PILO-induced SE of 7.5 min duration whereas 50 and 25% of the rats exposed to seizure durations of 30 and 120 min expressed motor seizures. Significant alterations reflecting hyperexcitability (increased number of population spikes (PSs)) and reduced paired-pulse inhibition were observed in recordings of hippocampal field potentials from rats with PILO-induced SE of at least 30 min duration. This was substantiated by brain lesions (necrosis in olfactory cortex, hippocampus, amygdala and thalamus) in all rats manifesting a SE of at least 30 min duration. Thus, the results of the present study demonstrate that rats exposed to PILO-induced SE of at least 30 min duration manifest an epileptogenic process, revealed 3 weeks later by several parameters. Among these, hippocampal field potentials appear to represent the most sensitive marker, potentially useful for pharmacological evaluation of drugs with putative antiepileptogenic properties.

摘要

本研究对不同持续时间的匹鲁卡品(PILO)诱导的癫痫持续状态(SE)所致大鼠脑电生理和神经病理学变化进行了表征。通过腹腔注射给予PILO(375mg/kg)诱导SE,在SE继发全身性发作开始后7.5、15、30、60或120分钟,静脉注射一剂地西泮(10mg/kg)终止发作。三周后,与对照组相比,暴露于持续30分钟或更长时间的PILO诱导SE的大鼠体重增加显著减少。持续7.5分钟的PILO诱导SE的大鼠未检测到自发性癫痫发作,而暴露于30分钟和120分钟癫痫发作持续时间的大鼠分别有50%和25%出现运动性癫痫发作。在至少持续30分钟的PILO诱导SE的大鼠海马场电位记录中,观察到反映兴奋性增高(群体峰电位(PSs)数量增加)和成对脉冲抑制降低的显著变化。这在所有表现出至少持续30分钟SE的大鼠脑损伤(嗅皮质、海马、杏仁核和丘脑坏死)中得到证实。因此,本研究结果表明,暴露于至少持续30分钟的PILO诱导SE的大鼠表现出癫痫发生过程,三周后通过几个参数得以揭示。其中,海马场电位似乎是最敏感的标志物,可能有助于对具有潜在抗癫痫发生特性的药物进行药理学评估。

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