Antiepileptic effects of levetiracetam in a rodent neonatal seizure model.
Antiepileptic effects of levetiracetam in a rodent neonatal seizure model.
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DOI：
10.1038/pr.2012.151
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发表时间：
2013-01
影响因子：
3.6
通讯作者：
Jensen FE
中科院分区：
文献类型：
--
作者：
Talos DM;Chang M;Kosaras B;Fitzgerald E;Murphy A;Folkerth RD;Jensen FE
新生儿癫痫发作可导致慢性癫痫和长期的行为和认知缺陷。左乙拉西坦（LEV）是一种与突触囊泡蛋白2A（SV 2A）结合的抗癫痫药物，已越来越多地用于治疗新生儿癫痫发作。缺乏关于LEV急性或长期疗效的临床前数据。我们测试了LEV在缺氧诱导的新生儿癫痫大鼠模型中的抗惊厥功效。此外，我们评估了出生后第10天（P）LEV治疗对晚年海人酸（KA）诱导的癫痫易感性和癫痫诱导的神经元损伤的保护作用。采用免疫印迹和免疫组织化学方法研究SV 2A在大鼠和人脑中的发育调控。LEV预处理在P10显着减少行为和电描记癫痫发作的累积持续时间在25和50 mg/kg。在P40，KA诱导的癫痫发作和神经元的损失显着减少在大鼠先前与LEV治疗。LEV靶SV 2A存在于新生大鼠和人脑中，并稳定增加至成年。LEV可抑制围产期缺氧引起的急性癫痫发作，并降低晚年癫痫发作的易感性和癫痫引起的神经元损伤，为疾病的改善提供了证据。这些结果支持考虑LEV在新生儿癫痫发作的临床试验。
Neonatal seizures can result in chronic epilepsy and long-term behavioral and cognitive deficits. Levetiracetam (LEV), an antiepileptic drug that binds to the synaptic vesicle protein 2A (SV2A), has been increasingly used off-label for the therapy of neonatal seizures. Preclinical data regarding the acute or long-term efficacy of LEV are lacking. We tested the anticonvulsant efficacy of LEV in a rat model of hypoxia-induced neonatal seizures. In addition, we evaluated the protective effects of postnatal day (P)10 LEV treatment on later-life kainic acid (KA)–induced seizure susceptibility and seizure-induced neuronal injury. Western blot and immunohistochemistry were used to assess the developmental regulation of SV2A in the rat and human brain. LEV pretreatment at P10 significantly decreased the cumulative duration of behavioral and electrographic seizures at both 25 and 50 mg/kg. At P40, KA-induced seizures and neuronal loss were significantly diminished in rats previously treated with LEV. LEV target SV2A is present in both neonatal rat and human brain and increases steadily to adulthood. LEV suppressed acute seizures induced by perinatal hypoxia and diminished later-life seizure susceptibility and seizure-induced neuronal injury, providing evidence for disease modification. These results support consideration of a clinical trial of LEV in neonatal seizures.
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影响因子：
3.1
作者：
Ramantani, Georgia;Ikonomidou, Chrysanthy;Dinger, Juergen
通讯作者：
Dinger, Juergen
影响因子：
5.6
作者：
Lukyanetz, EA;Shkryl, VM;Kostyuk, PG
通讯作者：
Kostyuk, PG
DOI：
10.1523/jneurosci.1734-08.2008
发表时间：
2008-08-06
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Rakhade SN;Zhou C;Aujla PK;Fishman R;Sucher NJ;Jensen FE
通讯作者：
Jensen FE
影响因子：
11.2
作者：
JENSEN, FE;APPLEGATE, CD;BURCHFIEL, JL
通讯作者：
BURCHFIEL, JL
DOI：
10.1111/j.1749-6632.2003.tb07517.x
发表时间：
2003-01-01
期刊：
NEUROPROTECTIVE AGENTS
影响因子：
--
作者：
Bittigau, P;Sifringer, M;Ikonomidou, C
通讯作者：
Ikonomidou, C