Administration of diazepam during status epilepticus reduces development and severity of epilepsy in rat
Administration of diazepam during status epilepticus reduces development and severity of epilepsy in rat
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DOI：
10.1016/j.eplepsyres.2004.10.003
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发表时间：
2005-01-01
影响因子：
2.2
通讯作者：
Nissinen, J
中科院分区：
文献类型：
--
作者：
Pitkänen, A;Kharatishvili, I;Nissinen, J
预防脑部损伤（例如癫痫持续状态（SE）、头部外伤或中风）后的癫痫发生仍然是一个挑战。即使癫痫无法预防，如果可以改变病理过程以减轻疾病的严重程度，也会是有益的。我们研究了早期停止 SE 是否会降低癫痫风险或导致病情较轻。电刺激杏仁核诱导 SE 引发癫痫发生。 SE 开始后 2 小时或 3 小时，用载体或地西泮（DZP，20 mg/kg）治疗动物（it = 72）。植入电极的未刺激大鼠作为组织学对照。所有动物在7-9周和11-15周后接受连续长期视频脑电图监测，以检测自发性癫痫发作的发生和严重程度。作为另一项结果测量，在组织学切片中评估海马损伤的严重程度。在媒介物组中，94%的动物出现癫痫。 DZP 治疗将 2 小时 DZP 组中癫痫动物的百分比降低至 42%，在 3 小时 DZP 组中降低至 71%（与赋形剂组相比，分别为 p < 0.001 和 p < 0.05）。如果发生癫痫，与赋形剂组相比，DZP 治疗动物的癫痫发作频率较低（中位癫痫发作/天），特别是 2 小时 DZP 组（中位癫痫发作/天）。最后，如果在 SE 后 2 小时而不是 3 小时开始 DZP 治疗，海马细胞损失的严重程度较对照组轻，苔藓纤维发芽的密度也低于载体组。这些数据表明，在 2 小时内用 DZP 治疗 SE 可以降低以后患癫痫的风险，而且如果出现癫痫，则症状较轻。 (C) 2004 Elsevier B.V. 保留所有权利。
Prevention of epileptogenesis after brain insults, such as status epilepticus (SE), head trauma, or stroke, remains a challenge. Even if epilepsy cannot be prevented, it would be beneficial if the pathologic process could be modified to result in a less severe disease. We examined whether early discontinuation of SE reduces the risk of epilepsy or results in milder disease. Epileptogenesis was triggered with SE induced by electrical stimulation of the amygdala. Animals (it = 72) were treated with vehicle or diazepam (DZP, 20 mg/kg) 2 h or 3 h after the beginning of SE. Electrode-implanted non-stimulated rats served as controls for histology. All animals underwent continuous long-term video-electroencephalography monitoring 7-9 weeks and 11-15 weeks later to detect the occurrence and severity of spontaneous seizures. As another outcome measure, the severity of hippocampal damage was assessed in histologic sections. In the vehicle group, 94% of animals developed epilepsy. DZP treatment reduced the percentage of epileptic animals to 42% in the 2-h DZP group and to 71% in the 3-h DZP group (p < 0.001 and p < 0.05 compared to the vehicle group, respectively). If epilepsy developed, the seizures were less frequent in DZP-treated animals compared to the vehicle group (median 16.4 seizures/day), particularly in the 2-h DZP group (median 0.4 seizures/day). Finally, if DZP treatment was started 2 h, but not 3 h after SE, the severity of hippocampal cell loss was milder and the density of mossy-fiber sprouting was lower than in the vehicle group. These data indicate that treatment of SE with DZP within 2 h reduces the risk of epilepsy later in life, and if epilepsy develops, it is milder. (C) 2004 Elsevier B.V. All rights reserved.