静脉注射左乙拉西坦在大鼠匹鲁卡品诱导的癫痫持续状态模型中的行为、生理和组织学研究。
Intravenous levetiracetam in the rat pilocarpine-induced status epilepticus model: behavioral, physiological and histological studies.
机构信息
Epilepsy Research Laboratory, Epilepsy Service and Neurology Service, Massachusetts General Hospital, Boston, MA 02114, USA.
出版信息
Neuropharmacology. 2010 Mar-Apr;58(4-5):793-8. doi: 10.1016/j.neuropharm.2009.12.007. Epub 2009 Dec 21.
PURPOSE
Status epilepticus is a neurological emergency associated with neuronal injury, lasting behavioral disturbance, and a high rate of mortality. Intravenous levetiracetam (LEV), an anti-epileptic drug approved to treat partial seizures, has recently been introduced. We sought to determine the effect of LEV administered intravenously in a chemoconvulsant model of status epilepticus.
METHODS
We examined the effect of intravenous LEV in the rat lithium-pilocarpine model of status epilepticus. Ten or 30 min after the onset of behavioral status epilepticus, animals were treated with LEV (200-1200 mg/kg i.v.) administered in a single bolus. Behavioral responses were recorded. Selected animals had continuous EEG recording before, during and after the administration of LEV. Some animals were sacrificed 24 h after the experiment and processed for histochemical assessment of neuronal injury.
RESULTS
When administered 30 min after the onset of behavioral epileptic seizures, transient attenuation of ictal behavior was observed in animals treated with 800 mg/kg or more of LEV. The duration of behavioral attenuation increased sharply as the dose rose to 1000 mg/kg or higher, from a mean of 4-23.6 min. When administered 10 min after seizure onset, 400 mg/kg of LEV resulted in transient ictal behavioral attenuation, and higher doses caused relatively longer periods of attenuation. Pretreatment with LEV prior to pilocarpine also delayed the onset of seizures. EEG recordings, however, showed no significant attenuation of ictal discharge. By contrast, TUNEL staining demonstrated less neuronal injury in hippocampii and other limbic structures in animals that responded behaviorally to LEV.
CONCLUSIONS
Intravenous administration of LEV in a chemoconvulsant model of status epilepticus results in attenuation of behavioral manifestations of seizure discharge and in reduction of neuronal injury but does not significantly alter ictal discharge recorded by EEG.
目的
癫痫持续状态是一种与神经元损伤相关的神经急症，持续存在行为障碍，死亡率高。静脉用左乙拉西坦（LEV）是一种抗癫痫药物，最近被批准用于治疗部分性发作。我们旨在确定静脉内给予 LEV 在癫痫持续状态的化学诱导模型中的作用。
方法
我们检查了静脉内 LEV 在大鼠锂-匹罗卡品癫痫持续状态模型中的作用。在行为性癫痫持续状态发作后 10 或 30 分钟，动物用静脉内给予的 LEV（200-1200mg/kg）单次推注治疗。记录行为反应。选择的动物在给予 LEV 前后进行连续 EEG 记录，以及之后。一些动物在实验后 24 小时被处死，并进行神经元损伤的组织化学评估。
结果
当在行为性癫痫发作开始后 30 分钟给予时，用 800mg/kg 或更高剂量的 LEV 治疗的动物观察到癫痫发作行为的短暂衰减。随着剂量增加到 1000mg/kg 或更高，行为衰减的持续时间急剧增加，从平均 4-23.6 分钟。当在癫痫发作开始后 10 分钟给予时，400mg/kg 的 LEV 导致短暂的癫痫发作行为衰减，较高剂量导致相对较长的衰减期。在给予匹罗卡品之前给予 LEV 预处理也延迟了癫痫发作的开始。然而，EEG 记录显示癫痫发作放电没有明显衰减。相比之下，TUNEL 染色显示在对 LEV 有行为反应的动物的海马和其他边缘结构中神经元损伤较少。
结论
在癫痫持续状态的化学诱导模型中静脉内给予 LEV 导致癫痫发作放电的行为表现衰减和神经元损伤减少，但对 EEG 记录的癫痫发作放电没有显著改变。
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