Long-term effects of neonatal seizures: a behavioral, electrophysiological, and histological study
Long-term effects of neonatal seizures: a behavioral, electrophysiological, and histological study
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DOI：
10.1016/s0165-3806(99)00135-2
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发表时间：
1999-12-10
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：
Huang, LT;Cilio, MR;Holmes, GL
以往的研究表明，在新生儿期反复发作导致癫痫发作阈值和学习记忆的永久性变化。这些变化的病理生理机制尚不清楚。为了确定新生儿癫痫发作是否会引起海马兴奋性或抑制性的变化，我们在出生后的前10天内对大鼠进行了50次氟乙烯诱导的癫痫发作（每天5次癫痫发作）。当大鼠成年后，我们使用氟乙醇吸入法检查癫痫发作阈值，并在水迷宫中检查学习和记忆。在不同的动物组中，我们评估了在体内配对脉冲的促进和抑制，无论是在CA1与刺激的Schaffer侧支或齿状回与刺激的perforant path.Following这些研究，动物被处死，并评估大脑苔藓纤维发芽与Timm染色。与对照动物相比，50次氟乙酸癫痫发作的大鼠具有降低的癫痫发作阈值，在水迷宫中的学习和记忆受损，以及齿状回的CA3锥体细胞层和分子层中的苔藓纤维发芽。氟乙烯处理组和对照组大鼠的成对脉冲抑制受损无显著差异。本研究表明，反复发作的新生儿癫痫发作导致神经元连接的变化和癫痫发作的易感性，学习和记忆的改变。然而，50次癫痫发作后的损伤程度是适度的，这表明未成熟的大脑对癫痫引起的损伤具有显著的弹性。(C)1999 Elsevier Science B.V.保留所有权利。
Previous studies have demonstrated that recurrent seizures during the neonatal period lead to permanent changes in seizure threshold and learning and memory. The pathophysiological mechanisms for these changes are not clear. To determine if neonatal seizures cause changes in hippocampal excitability or inhibition, we subjected rats to 50 flurothyl-induced seizures during the first 10 days of Life (five seizures per day). When the rats were adults, we examined seizure threshold using flurothyl inhalation, and learning and memory in the water maze. in separate groups of animals, we evaluated in vivo paired-pulse facilitation and inhibition in either CA1 with stimulation of the Schaffer collaterals or dentate gyrus with stimulation of the perforant path. Following these studies, the animals were sacrificed and the brains evaluated for mossy fiber sprouting with the Timm stain. Compared to control animals, rats with 50 flurothyl seizures had a reduced seizure threshold, impaired learning and memory in the water maze, and sprouting of mossy fibers in the CA3 pyramidal cell layer and molecular layer of the dentate gyrus. No significant differences in impaired paired-pulse inhibition was noted between the flurothyl-treated and control rats. This study demonstrates that recurrent neonatal seizures result in changes of neuronal connectivity and alterations in seizure susceptibility, learning and memory. However, the degree of impairment following 50 seizures was modest, demonstrating that the immature brain is remarkably resilient to seizure-induced damage. (C) 1999 Elsevier Science B.V. All rights reserved.