Do proconvulsants modify or halt epileptogenesis? Pentylenetetrazole is ineffective in two rat models of temporal lobe epilepsy
Do proconvulsants modify or halt epileptogenesis? Pentylenetetrazole is ineffective in two rat models of temporal lobe epilepsy
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促惊厥药会改变或阻止癫痫发生吗？
DOI：
10.1111/j.1460-9568.2012.08143.x
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发表时间：
2012
影响因子：
3.4
通讯作者：
W Löscher
中科院分区：
文献类型：
--
作者：
Rattka M;Brandt C;W Löscher
对于在最初的脑部突发性损伤后有发生癫痫风险的患者，致癫痫潜伏期可能为开始潜在的抗癫痫治疗以试图预防癫痫的发展提供了机会。抗癫痫发生的一个潜在目标是潜伏期神经元过度兴奋的发展。令人惊讶的是，最近对颞叶癫痫（TLE）模型的一些研究表明促惊厥药物可能对癫痫发生产生有利影响，从而提出了对癫痫发生进行促惊厥预防的建议。在本研究中，我们通过在大鼠海马内红藻氨酸模型和锂-毛果芸香碱模型这两种 TLE 模型中使用 GABAA 受体拮抗剂戊四唑 (PTZ) 进行实验来评估这一具有启发性的假设。首先，我们通过静脉注射反复确定 PTZ 癫痫阈值。在海马内红藻氨酸后的潜伏期输注惊厥药。与最近在锂-毛果芸香碱模型中进行的实验一致，在癫痫持续状态后的几天内，PTZ 癫痫阈值显着降低。然后，我们研究了红藻氨酸或毛果芸香碱后不同时间长时间输注促惊厥剂量的 PTZ 是否会影响癫痫的发展。 PTZ 不能阻止自发性复发性癫痫发作的发展，也不能降低其频率或严重程度，但仅发挥中等的疾病缓解作用，因为红藻氨酸模型中的自发性癫痫发作显着缩短。这些数据表明，在 SE 后的潜伏期使用促惊厥药物（如 PTZ）并不是一种有前景的预防癫痫策略。
In patients at risk of developing epilepsy after an initial precipitating injury to the brain, the epileptogenic latent period may offer a window of opportunity for initiating potential antiepileptogenic therapy in an attempt to prevent epilepsy from developing. One potential target for antiepileptogenesis is the development of neuronal hyperexcitability during the latent period. Surprisingly, some recent studies in models of temporal lobe epilepsy (TLE) have suggested that proconvulsant drugs could have favourable effects on epileptogenesis, resulting in the proposal of pursuing proconvulsant prophylaxis for epileptogenesis. In the present study, we evaluated this provocative hypothesis by experiments with the GABAAreceptor antagonist pentylenetetrazole (PTZ) in two TLE models, the intrahippocampal kainate model and the lithium–pilocarpine model in rats. First, we repeatedly determined the PTZ seizure threshold by i.v. infusion of the convulsant during the latent period following intrahippocampal kainate. In line with recent experiments in the lithium–pilocarpine model, the PTZ seizure threshold was significantly decreased over several days following status epilepticus. We then studied whether prolonged infusion of a proconvulsant dose of PTZ at different times after kainate or pilocarpine affected the development of epilepsy. PTZ did not prevent the development of spontaneous recurrent seizures and did not decrease their frequency or severity, but exerted only a moderate disease‐modifying effect in that spontaneous seizures in the kainate model were significantly shortened. These data indicate that administration of proconvulsant drugs such as PTZ during the latent period following SE is not a promising strategy for preventing epilepsy.
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影响因子：
2.2
作者：
Pitkänen, A;Narkilahti, S;Nissinen, J
通讯作者：
Nissinen, J
雌性大鼠生殖的神经生物学
DOI：
10.1007/978-3-642-83797-5
发表时间：
1989
期刊：
Alcoholism, clinical and experimental research
影响因子：
--
作者：
J. Everett
通讯作者：
J. Everett
DOI：
--
发表时间：
1985
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
Ramzan,IM;Levy,G
通讯作者：
Levy,G
影响因子：
4.8
作者：
Mann, Edward O.;Mody, Istvan
通讯作者：
Mody, Istvan
DOI：
10.1016/0013-4694(72)90177-0
发表时间：
1972-01-01
期刊：
ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY
影响因子：
--
作者：
RACINE, RJ
通讯作者：
RACINE, RJ