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持续惊厥性癫痫发作的持续时间决定了大鼠海马神经发生的模式和自发性癫痫的发展。

The duration of sustained convulsive seizures determines the pattern of hippocampal neurogenesis and the development of spontaneous epilepsy in rats.

机构信息

Institute of Physiology, National Yang-Ming University, Taipei, Taiwan.

出版信息

Epilepsy Res. 2012 Feb;98(2-3):206-15. doi: 10.1016/j.eplepsyres.2011.09.015. Epub 2011 Oct 19.

DOI:10.1016/j.eplepsyres.2011.09.015
PMID:22014748
Abstract

The duration of sustained seizures (SS) plays a crucial role in the occurrence of spontaneous recurrent seizures (SRS) in experimental animals. We tested whether rats with varying durations of initial convulsive SS exhibited differential neurogenesis patterns in the hippocampal dentate gyrus that may be related to subsequent epileptogenesis. Sprague-Dawley rats with pilocarpine-induced convulsive SS were divided into short SS (30 min) and long SS (2 h) groups. Their behavior was monitored to identify convulsive SRS. From 1 to 28 days post-SS, cell proliferation was evaluated by 5'-bromo-2'-deoxyuridine (BrdU) labeling and immature neuroblasts in the dentate gyrus were identified by doublecortin immunohistochemistry. Convulsive SRS was detected in 8 out of the 9 long SS rats, but not in the 9 short SS rats. During day 1-3, proliferative cells were diffusely localized throughout the hippocampus in the long SS rats but were primarily confined within the subgranular zone in the short SS rats. Within the subgranular zone, a significant increase in the number of BrdU-positive cells was found at days 3 and 7 after the long SS and on day 1 after the short SS. Notably, abnormal dendritic outgrowth and hilar-ectopic localization of doublecortin-positive cells were present in the long SS rats. In conclusion, aberrant hippocampal neurogenesis following long SS may contribute to the development of SRS.

摘要

持续癫痫发作(SS)的持续时间在实验动物自发性反复癫痫发作(SRS)的发生中起着至关重要的作用。我们测试了初始惊厥性 SS 持续时间不同的大鼠是否在海马齿状回中表现出不同的神经发生模式,这可能与随后的癫痫发生有关。用匹罗卡品诱导惊厥性 SS 的 Sprague-Dawley 大鼠分为短 SS(30 分钟)和长 SS(2 小时)组。监测它们的行为以识别惊厥性 SRS。在 SS 后 1 至 28 天,通过 5'-溴-2'-脱氧尿苷(BrdU)标记评估细胞增殖,并通过双皮质素免疫组织化学鉴定齿状回中的未成熟神经母细胞。在 9 只长 SS 大鼠中有 8 只检测到惊厥性 SRS,但在 9 只短 SS 大鼠中没有检测到。在第 1-3 天,增殖细胞在长 SS 大鼠的海马中弥漫定位,但在短 SS 大鼠中主要局限于颗粒下区。在颗粒下区,在长 SS 后第 3 天和第 7 天以及短 SS 后第 1 天,BrdU 阳性细胞数量显著增加。值得注意的是,长 SS 大鼠存在异常树突状生长和双皮质素阳性细胞的门齿异位定位。总之,长 SS 后海马异常神经发生可能有助于 SRS 的发展。

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