Consequences of neonatal seizures in the rat: Morphological and behavioral effects

Consequences of neonatal seizures in the rat: Morphological and behavioral effects
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DOI:
10.1002/ana.410440602
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发表时间:
1998-12-01
影响因子:
11.2
通讯作者:
Ben-Ari, Y
Ben-Ari, Y
中科院分区:
医学1区
文献类型:
--
作者:
Holmes, GL;Gairsa, JL;Ben-Ari, Y

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尽管新生儿癫痫发作是不良神经预后的一个预测指标,但关于癫痫发作是否仅仅反映了潜在的脑损伤或可能导致损害存在争议。我们对新生大鼠进行了25次氟乙基诱发的癫痫发作。成年后,将其与对照组进行空间学习和活动水平的比较。通过完整海马形成准备评估复发性癫痫发作对海马兴奋的短期影响,通过评估癫痫阈值评估长期影响,分析大脑的神经元丢失、颗粒细胞轴突(苔藓纤维)的发芽和神经发生。与对照组相比,遭受新生儿癫痫发作的大鼠学习能力受损,活动水平下降。在完整的海马准备中,配对脉冲兴奋或抑制或后放电持续时间没有差异。然而,当对成年大鼠进行研究时,反复发作氟醚发作的大鼠对戊四氮的发作阈值明显低于对照组。与对照组相比,反复发作的大鼠有更多的齿状颗粒细胞和更多新形成的颗粒细胞。反复发作的大鼠在CA3和核上区也有苔藓纤维的萌发。新生儿期反复发作的短暂发作对行为、发作易感性和大脑发育有长期的有害影响。
Whereas neonatal seizures are a predictor of adverse neurological outcome, there is controversy regarding whether seizures simply reflect an underlying brain injury or can cause damage. We subjected neonatal rats to a series of 25 brief flurothyl-induced seizures. Once mature the rats were compared with control littermates for spatial learning and activity level. Short-term effects of recurrent seizures on hippocampal excitation were assessed by using the intact hippocampus formation preparation and long-term effects by assessing seizure threshold Brains were analyzed for neuronal loss, sprouting of granule cell axons (mossy fibers), and neurogenesis. Compared with controls, rats subjected to neonatal seizures had impaired learning and decreased activity levels. There were no differences in paired-pulse excitation or inhibition or duration of afterdischarges in the intact hippocampal preparation. However, when studied as adults, rats with recurrent flurothyl seizures had a significantly lower seizure threshold to pentylenetetrazol than controls. Rats with recurrent seizures had greater numbers of dentate granule cells and more newly formed granule cells than the controls. Rats with recurrent seizures also had sprouting of mossy fibers in CA3 and the supragranular region. Recurrent brief seizures during the neonatal period have long-term detrimental effects on behavior, seizure susceptibility, and brain development.