Antiepileptogenesis Therapy with Levetiracetam: Data from Kindling versus Status Epilepticus Models.
Antiepileptogenesis Therapy with Levetiracetam: Data from Kindling versus Status Epilepticus Models.
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DOI：
10.1111/j.1535-7511.2007.00226.x
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发表时间：
2008-01-01
影响因子：
3.6
通讯作者：
Staley, Kevin J
中科院分区：
文献类型：
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作者：
Dudek, F Edward;Bertram, Edward H;Staley, Kevin J
左乙拉西坦在癫痫持续状态后的预防治疗：对癫痫的发生、神经元损伤和行为改变缺乏作用.北京：神经药理学杂志，2007；53(2)：207-221.左乙拉西坦(Lev)是一种结构新颖的抗癫痫药物，在实验和临床研究中都显示了广泛的抗癫痫活性。之前在点燃模型中的实验表明，LEV除了具有抑制癫痫发作的活性外，还可能具有抗癫痫或改善疾病的活性。在本研究中，我们使用了一种大鼠模型，在该模型中，持续电刺激杏仁核诱发癫痫持续状态(SE)后，出现自发性反复发作(SRS)、行为改变和海马区损害的癫痫模型，评估了这种可能性。使用了两种实验方案。在第一个方案中，LEV治疗在杏仁核电刺激开始后24小时开始，而不事先终止SE。在第二种方案中，在4h后用安定阻断SE，然后立即开始用LEV治疗。SE后继续用LEV治疗8周(实验1)或5周(实验2)，通过渗透压泵持续给药。记录治疗过程中和治疗后SRS的发生情况。此外，这些大鼠还接受了一系列行为测试，包括高架加迷宫和莫里斯水迷宫。最后，对动物的大脑进行了海马体结构的组织学损伤分析。在为这些实验选择的实验方案中，LEV没有发挥抗癫痫或神经保护作用。此外，癫痫大鼠的行为改变，如行为高兴奋性和学习障碍，不受SE后LEV治疗的影响。这些数据不支持这样一种观点，即SE后给予LEV可以防止或减少大鼠在这种大脑侮辱后发生的长期变化。
Prophylactic Treatment with Levetiracetam after Status Epilepticus: Lack of Effect on Epileptogenesis, Neuronal Damage, and Behavioral Alterations in Rats.Brandt C, Glien M, Gastens AM, Fedrowitz M, Bethmann K, Volk HA, Potschka H, Löscher W.Neuropharmacology2007;53(2):207–221. Levetiracetam (LEV) is a structurally novel antiepileptic drug (AED) which has demonstrated a broad spectrum of anticonvulsant activities both in experimental and clinical studies. Previous experiments in the kindling model suggested that LEV, in addition to its seizure-suppressing activity, may possess antiepileptogenic or disease-modifying activity. In the present study, we evaluated this possibility by using a rat model in which epilepsy with spontaneous recurrent seizures (SRS), behavioral alterations, and hippocampal damages develop after a status epilepticus (SE) induced by sustained electrical stimulation of the basal amygdala. Two experimental protocols were used. In the first protocol, LEV treatment was started 24h after onset of electrical amygdala stimulation without prior termination of the SE. In the second protocol, the SE was interrupted after 4h by diazepam, immediately followed by onset of treatment with LEV. Treatment with LEV was continued for 8weeks (experiment #1) or 5weeks (experiment #2) after SE, using continuous drug administration via osmotic minipumps. The occurrence of SRS was recorded during and after treatment. In addition, the rats were tested in a battery of behavioral tests, including the elevated-plus maze and the Morris water maze. Finally, the brains of the animals were analyzed for histological lesions in the hippocampal formation. With the experimental protocols chosen for these experiments, LEV did not exert antiepileptogenic or neuroprotective activity. Furthermore, the behavioral alterations, e.g., behavioral hyperexcitability and learning deficits, in epileptic rats were not affected by treatment with LEV after SE. These data do not support the idea that administration of LEV after SE prevents or reduces the long-term alterations developing after such brain insult in rats.