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单次戊四氮诱导的强直阵挛性发作发作伴随着大鼠认知功能的缓慢下降。

A single pentylenetetrazole-induced clonic-tonic seizure episode is accompanied by a slowly developing cognitive decline in rats.

机构信息

Department of Functional Biochemistry of the Nervous System, Institute of Higher Nervous Activity and Neurophysiology, RAS, Butlerov Street 5A, Moscow 117485, Russia.

出版信息

Epilepsy Behav. 2013 Feb;26(2):196-202. doi: 10.1016/j.yebeh.2012.12.006. Epub 2013 Jan 11.

Abstract

According to different studies, between 5% and 10% of people suffer a single isolated seizure episode at some time in their life. However, little is known about the effects of a single seizure episode on cognitive function, and clinical investigations of this issue are not easy to perform. In this situation, animal models may be a reasonable choice. The aim of our study was to follow the time course of delayed effects of generalized clonic-tonic convulsions on learning and memory functions in rats. A clonic-tonic seizure episode was induced by a single i.p. injection of pentylenetetrazole (70 mg/kg). Different behavioral tests were performed between days 10 and 100 after the convulsant administration. A single seizure episode resulted in a gradual decline in short-term memory function as assessed by novel object recognition and social recognition tests. The seizure episode induced a quick increase in hippocampal cell proliferation; however, the excessive newly generated cells seemed to be eliminated by the time of obvious cognitive impairment. These observations are indicative of a slowly developing and long-lasting influence of a single seizure episode on cognitive function. A rather long time period between the seizure episode and the manifestations of cognitive decline provides a window for a possible therapeutic intervention, and an elaboration of such "post-conditioning" treatments may be a promising opportunity to prevent subsequent mental impairments in patients.

摘要

根据不同的研究,一生中,有 5%至 10%的人会经历一次单一的孤立性癫痫发作。然而,人们对单次癫痫发作对认知功能的影响知之甚少,且对此问题的临床研究也不易进行。在这种情况下,动物模型可能是一个合理的选择。我们的研究目的是跟踪全身性强直阵挛性癫痫发作对大鼠学习和记忆功能的延迟影响的时间进程。通过单次腹腔注射戊四氮(70mg/kg)诱导强直阵挛发作。在致痫剂给药后 10 至 100 天之间进行不同的行为测试。单次癫痫发作导致短期记忆功能逐渐下降,通过新物体识别和社会识别测试进行评估。癫痫发作引起海马细胞增殖迅速增加;然而,在明显认知障碍出现时,过多的新生细胞似乎被清除。这些观察结果表明单次癫痫发作对认知功能有一个缓慢发展和持久的影响。癫痫发作和认知能力下降之间的时间间隔较长,为可能的治疗干预提供了一个窗口,并且详细阐述这种“后处理”治疗可能是预防患者随后精神障碍的一个有前途的机会。

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