A model of posttraumatic epilepsy induced by lateral fluid-percussion brain injury in rats
A model of posttraumatic epilepsy induced by lateral fluid-percussion brain injury in rats
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DOI：
10.1016/j.neuroscience.2006.03.012
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发表时间：
2006-01-01
期刊：
影响因子：
3.3
通讯作者：
Pitkanen, A.
中科院分区：
文献类型：
--
作者：
Kharatishvili, I.;Nissinen, J. P.;Pitkanen, A.
虽然创伤性脑损伤是症状性癫痫的主要原因，但其导致复发性癫痫发作的机制尚不清楚。创伤后癫痫的动物模型，可靠地再现人类创伤性脑损伤的临床后遗症是必不可少的，以确定创伤后癫痫发生的分子和细胞底物，并进行临床前筛选的新的抗癫痫化合物。我们研究了大鼠严重的非穿透性侧面液压冲击脑损伤诱发的外伤后癫痫的电生理、行为和结构特征。两项独立实验的数据表明，43%至50%的受伤动物出现癫痫，潜伏期在7周到1年之间。平均癫痫发作频率为每天0.3 +/- 0.2次癫痫发作，平均癫痫发作持续时间为113 +/- 46 s。在大多数动物中，行为性癫痫发作的严重程度随时间推移而增加。继发性全身性癫痫发作占所有癫痫发作的平均66 +/- 37%。与无癫痫的创伤性脑损伤动物相比，创伤后癫痫动物同侧海马苔藓纤维发芽增加。体视学细胞计数表明，创伤性脑损伤后，同侧齿状门神经元丢失。我们的数据表明，创伤后癫痫的发生率为40%至50%，严重的非穿透性液压冲击脑损伤后，大鼠，侧位液压冲击模型可以作为一个临床相关的工具，病理生理学和临床前研究。(c)2006年IBRO。由爱思唯尔有限公司出版。保留所有权利。
Although traumatic brain injury is a major cause of symptomatic epilepsy, the mechanism by which it leads to recurrent seizures is unknown. An animal model of posttraumatic epilepsy that reliably reproduces the clinical sequelae of human traumatic brain injury is essential to identify the molecular and cellular substrates of posttraumatic epileptogenesis, and perform preclinical screening of new antiepileptogenic compounds. We studied the electrophysiologic, behavioral, and structural features of posttraumatic epilepsy induced by severe, non-penetrating lateral fluid-percussion brain injury in rats. Data from two independent experiments indicated that 43% to 50% of injured animals developed epilepsy, with a latency period between 7 weeks to 1 year. Mean seizure frequency was 0.3 +/- 0.2 seizures per day and mean seizure duration was 113 +/- 46 s. Behavioral seizure severity increased over time in the majority of animals. Secondarily-generalized seizures comprised an average of 66 +/- 37% of all seizures. Mossy fiber sprouting was increased in the ipsilateral hippocampus of animals with posttraumatic epilepsy compared with those subjected to traumatic brain injury without epilepsy. Stereologic cell counts indicated a loss of dentate hilar neurons ipsilaterally following traumatic brain injury. Our data suggest that posttraumatic epilepsy occurs with a frequency of 40% to 50% after severe non-penetrating fluid-percussion brain injury in rats, and that the lateral fluid percussion model can serve as a clinically-relevant tool for pathophysiologic and preclinical studies. (c) 2006 IBRO. Published by Elsevier Ltd. All rights reserved.