Timing of cognitive deficits following neonatal seizures: relationship to histological changes in the hippocampus
Timing of cognitive deficits following neonatal seizures: relationship to histological changes in the hippocampus
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DOI：
10.1016/s0165-3806(01)00265-6
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发表时间：
2001-11-26
期刊：
影响因子：
--
通讯作者：
Holmes, GL
中科院分区：
文献类型：
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作者：
Sogawa, Y;Monokoshi, M;Holmes, GL
新生儿癫痫发作经常与认知障碍和癫痫发作阈值降低有关。我们实验室以前的研究表明，反复发作的新生癫痫大鼠成年后学习障碍，癫痫阈值降低，CA3区和海马齿状回颗粒上区苔藓纤维萌发。本研究的目的是确定反复发作的新生大鼠认知功能障碍的发病年龄和癫痫敏感性的改变，以及这种认知障碍与苔藓纤维发芽和谷氨酸受体表达的关系。从出生后第0天开始，大鼠在9天的时间内暴露于45次氟乙基诱发癫痫发作。在P20或P35时对不同亚组大鼠在水迷宫中的视觉空间学习和癫痫敏感性进行评估。在相同的时间点评估脑细胞丢失、苔藓纤维分布以及AMPA(GluR1)和NMDA(NMDAR1)亚受体的表达。新生癫痫大鼠在P20和P35表现出显著的水迷宫表现和增加的癫痫敏感度。P20和P35均可见苔藓纤维发芽进入齿状回CA3区和颗粒上区。在P20时，GluR1在CA3中表达增加，在P35时，NMDAR1在CA3和齿状回颗粒上区表达增加。我们的发现表明，在一系列新生儿癫痫发作后，在脱机前就会发生癫痫易感性和认知障碍的改变。此外，这些认知和癫痫敏感性的改变与苔藓纤维的萌发和谷氨酸受体表达的增加是平行的。为了有效，我们的结果表明，改变新生儿癫痫发作后不良后果的策略必须在癫痫发作期间或之后不久启动。(C)2001年，爱思唯尔科学公司出版。
Neonatal seizures are frequently associated with cognitive impairment and reduced seizure threshold. Previous studies in our laboratory have demonstrated that rats with recurrent neonatal seizures have impaired learning, lower seizure thresholds, and sprouting of mossy fibers in CA3 and the supragranular region of the dentate gyrus in the hippocampus when studied as adults. The goal of this study was to determine the age of onset of cognitive dysfunction and alterations in seizure susceptibility in rats subjected to recurrent neonatal seizures and the relation of this cognitive impairment to mossy fiber sprouting and expression of glutamate receptors. Starting at postnatal day (P) 0, rats were exposed to 45 flurothyl-induced seizures over a 9-day period of time. Visual-spatial learning in the water maze and seizure susceptibility were assessed in subsets of the rats at P20 or P35. Brains were evaluated for cell loss, mossy fiber distribution, and AMPA (GluR1) and NMDA (NMDAR1) subreceptor expression at these same time points. Rats with neonatal seizures showed significant impairment in the performance of the water maze and increased seizure susceptibility at both P20 and P35. Sprouting of mossy fibers into the CA3 and supragranular region of the dentate gyrus was seen at both P20 and P35. GluR1 expression was increased in CA3 at P20 and NMDAR1 was increased in expression in CA3 and the supragranular region of the dentate gyrus at P35. Our findings indicate that altered seizure susceptibility and cognitive impairment occurs prior to weaning following a series of neonatal seizures. Furthermore, these alterations in cognition and seizure susceptibility are paralleled by sprouting of mossy fibers and increased expression of glutamate receptors. To be effective, our results suggest that strategies to alter the adverse outcome following neonatal seizures will have to be initiated during, or shortly following, the seizures. (C) 2001 Published by Elsevier Science B.V.