Long-term effects of status epilepticus in the immature brain are specific for age and model

Long-term effects of status epilepticus in the immature brain are specific for age and model
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DOI:
10.1046/j.1528-1157.2003.48802.x
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发表时间:
2003-04-01
期刊:
影响因子:
5.6
通讯作者:
Holmes, GL
Holmes, GL
中科院分区:
医学1区
文献类型:
--
作者:
Cilio, MR;Sogawa, Y;Holmes, GL

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目的:癫痫持续状态(SE)在儿童中比成人更常见,并且具有较高的死亡率和发病率。成年大鼠的SE导致学习和记忆的长期障碍,以及对进一步癫痫发作的增强的癫痫发作易感性。相反,许多研究表明,未成熟的大脑是不太容易受到SE后的形态和生理变化。本研究的目的是确定发育过程中SE对海马可塑性和认知功能的长期影响是否具有年龄和模型特异性。本研究采用锂-匹罗卡品(Li-PC)在发育过程中的不同年龄点诱导SE(第12页、第16页、P20)并评估这种异常神经活动对动物在P55开始的空间记忆表现和癫痫易感性的影响,结果:我们证明,在P12时的SE不会导致成年时可检测到的任何结构或功能变化,而在P16和P20时的SE都会诱导海马内的细胞丢失和苔藓纤维发芽,并且当动物作为成年人进行测试时会导致认知障碍。而癫痫发作阈值全身性癫痫发作没有改变,在P20 SE的动物表现出增加的易感性点燃成年。
Purpose: Status epilepticus (SE) is more common in children than adults and has a high mortality and morbidity rate. SE in adult rats results in long-term disturbances in learning and memory, as well as an enhanced seizure susceptibility to further seizures. In contrast, a number of studies suggest that the immature brain is less vulnerable to the morphologic and physiologic alterations after SE. The goal of this study was to determine whether the long-term consequences of SE during development on hippocampal plasticity and cognitive function are age and model specific.Methods: We used lithium-pilocarpine (Li-PC) to induce SE at different age points during development (P12, P16, P20) and evaluated the effects of this abnormal neural activity on spatial memory performance and seizure susceptibility in the animals beginning at P55, corresponding to young adulthood.Results: We demonstrated that SE at P12 did not result in any structural or functional changes detectable in adulthood, whereas SE at both P16 and P20 induced cell loss and mossy fiber sprouting within the hippocampus and cognitive impairment when the animals were tested as adults.Conclusions: Whereas the seizure threshold to generalized seizures was not altered, animals with SE at P20 showed an increased susceptibility to kindling in adulthood.