Effect of lamotrigine treatment on epileptogenesis:: an experimental study in rat
Effect of lamotrigine treatment on epileptogenesis:: an experimental study in rat
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DOI：
10.1016/j.eplepsyres.2004.01.001
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发表时间：
2004-02-01
影响因子：
2.2
通讯作者：
Pitkänen, A
中科院分区：
文献类型：
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作者：
Nissinen, J;Large, CH;Pitkänen, A
在患有急性脑损伤性损伤（如癫痫持续状态（SE））的患者中预防癫痫发生是一项重大挑战。我们研究了在SE期间开始拉莫三嗪（LTG）治疗是否是抗癫痫或改善疾病。为了模拟临床研究设计，在14只大鼠中开始电诱导SE后2小时开始LTG治疗（20 mg/kg），并持续11周（每天20 mg/kg持续2周，然后每天10 mg/kg持续9周）。一组大鼠（n = 14）用溶剂处理。9只接受溶剂处理的未刺激大鼠作为对照。结果指标为癫痫发生率、癫痫严重程度和组织学（神经元丢失、苔藓纤维发芽）。在SE后第11周（即治疗期间）和第14周（即药物洗脱后），通过1周连续视频脑电图监测评估癫痫发作的临床发生率。LTG可使SE时电图发作次数减少至溶剂组的43%（P <0.05）。在溶剂组中，93%（13/14）的动物和在LTG组中，100%（14/14）的动物发生癫痫。在两组中，64%的大鼠有严重的癫痫（发作频率> 1/天）。自发性癫痫发作的平均频率、癫痫发作持续时间或癫痫发作的行为严重程度在组间没有差异。海马神经元损伤程度和苔藓纤维出芽密度相似。然而，在患有严重癫痫的LTG治疗大鼠中，癫痫发作的持续时间较短（34秒对54秒）。LTG治疗期间行为发作评分较药物洗脱后轻（1.4比3.4，P <0.05）。在SE期间开始LTG治疗并持续11周，LTG治疗不是抗癫痫的，但不会使结局恶化。这些数据，加上其他抗癫痫药物的早期研究，建议其他的策略比钠通道阻滞剂应探讨调制的分子级联反应导致癫痫发作后SE。(C)2004 Elsevier B.V.保留所有权利。
Prevention of epileptogenesis in patients with acute brain damaging insults like status epilepticus (SE) is a major challenge. We investigated whether lamotrigine (LTG) treatment started during SE is antiepileptogenic or disease-modifying. To mimic a clinical study design, LTG treatment (20 mg/kg) was started 2 h after the beginning of electrically induced SE in 14 rats and continued for I I weeks (20 mg/kg per day for 2 weeks followed by 10 mg/kg per day for 9 weeks). One group of rats (n = 14) was treated with vehicle. Nine non-stimulated rats with vehicle treatment served as controls. Outcome measures were occurrence of epilepsy, severity of epilepsy, and histology (neuronal loss, mossy fiber sprouting). Clinical occurrence of seizures was assessed with 1-week continuous video-electroencephalography monitoring during the 11th (i.e. during treatment) and 14th week (i.e. after drug wash-out) after SE. LTG reduced the number of electrographic seizures during SE to 43% of that in the vehicle group (P < 0.05). In the vehicle group, 93% (13/14), and in the LTG group, 100% (14/14) of the animals, developed epilepsy. In both groups, 64% of the rats had severe epilepsy (seizure frequency >1 per day). The mean frequency of spontaneous seizures, seizure duration, or behavioral severity of seizures did not differ between groups. The severity of hippocampal neuronal damage and density of mossy fiber sprouting were similar. In LTG-treated rats with severe epilepsy, however, the duration of seizures was shorter (34 versus 54 s. P < 0.05) and the behavioral seizure score was milder (1.4 versus 3.4, P < 0.05) during LTG treatment than after drug wash-out. LTG treatment started during SE and continued for I I weeks was not antiepileptogenic but did not worsen the outcome. These data, together with earlier studies of other antiepileptic drugs, suggest that strategies other than Na+-channel blockade should be explored to modulate the molecular cascades leading to epileptogenesis after SE. (C) 2004 Elsevier B.V. All rights reserved.