Disruption of cortical development as a consequence of repetitive pilocarpine-induced status epilepticus in rats
Disruption of cortical development as a consequence of repetitive pilocarpine-induced status epilepticus in rats
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DOI：
10.1111/j.1528-1167.2005.01003.x
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发表时间：
2005-01-01
期刊：
影响因子：
5.6
通讯作者：
Spreafico, R
中科院分区：
文献类型：
--
作者：
da Silva, AV;Regondi, TC;Spreafico, R
目的：本研究的目的是观察可能的皮质异常后，反复匹罗卡品诱导癫痫持续状态（SE）在大鼠发育过程中。方法：Wistar大鼠于P7、P8、P9腹腔注射2%盐酸毛果芸香碱380 mg/kg。所有实验大鼠在注射毛果芸香碱后均表现出SE。在P10和P35处死大鼠，并使用抗非磷酸化神经丝（SMI-311）、小白蛋白（PV）、钙结合蛋白（CB）、钙视网膜蛋白（CR）和谷氨酸脱羧酶（GAD-65）的抗体，在50 μ m振动切片机上进行免疫细胞化学程序。选择的切片用于TUNEL法和双标记实验，使用相同标记物的不同混合物。结果：本工作的主要发现是（a）改变皮质内回路的发育;（B）新皮质中间神经元中PV免疫反应的预期;（c）增加GAD-65免疫反应;和（d）减少新皮质凋亡过程。从这些结果中，我们认为，以前健康的大脑，没有遗传异常，可能会开发一个“获得性”的皮质发育中断，其演变再现与认知障碍相关的儿童癫痫的一些特征。关键词：未成熟脑-早期损伤-凋亡-新皮质-中间神经元
Purpose: The aim of the present study was to observe possible cortical abnormalities after repetitive pilocarpine-induced status epilepticus (SE) in rats during development. Methods: Wistar rats received intraperitoneal injection of pilocarpine hydrochloride 2% (380 mg/kg) at P7, P8, and P9. All experimental rats displayed SE after pilocarpine injections. Rats were killed at P10 and P35, and immunocytochemistry procedures were performed on 50-mu m vibratome sections, by using antibodies against nonphosphorylated neurofilament(SMI-311), parvalburnin (PV), calbindin (CB), calretinin (CR), and glutamate decarboxylase (GAD-65). Selected sections were used for the TUNEL method and double-labeling experiments, with different mixtures of the same markers.Results: The major findings of the present work were (a) altered intracortical circuitry development; (b) anticipation of PV immunoreactivity in neocortical interneurons; (c) increased GAD-65 immunoreactivity; and (d) reduced neocortical apoptotic process.Conclusions: From these results, we suggest that previously healthy brain, without genetic abnormalities, might develop an "acquired" disruption of cortical development whose evolution reproduces some characteristics of the childhood epilepsies associated with cognitive impairment. Key Words: Immature brain-Early insult-Apoptosis-Neocortex-Interneurons.