The effect of levetiracetam on neuronal apoptosis in neonatal rat model of hypoxic ischemic brain injury
The effect of levetiracetam on neuronal apoptosis in neonatal rat model of hypoxic ischemic brain injury
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DOI：
10.1016/j.earlhumdev.2012.12.002
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发表时间：
2013-05-01
影响因子：
2.5
通讯作者：
Zorludemir, Suzan
中科院分区：
文献类型：
--
作者：
Kilicdag, Hasan;Daghoglu, Kenan;Zorludemir, Suzan
背景：缺氧缺血性脑损伤(HIBI)是新生儿死亡和发病的常见原因。左乙拉西坦(Lev)作为一种潜在的脑缺血神经保护药物，受到越来越多的关注，在癫痫的发生调控和神经保护中可能起到至关重要的作用。目的：探讨LEV对新生大鼠HIBI模型神经细胞凋亡的影响。方法：7日龄Wistar大鼠右侧颈总动脉结扎，低氧(92%氮气，8%氧气)2 h，缺氧后给予Lev或生理盐水治疗。假手术组大鼠既不结扎，也不缺氧。用末端脱氧核苷酸转移酶介导的dUTP缺口末端标记法(TUNEL)检测神经元的凋亡。结果：生理盐水治疗组大鼠海马区和大脑皮层的细胞凋亡率均明显高于假手术组。海马区和大脑皮层的细胞凋亡数与假手术组和利培酮治疗组相似。与生理盐水组相比，LEV治疗组神经细胞凋亡数明显减少。结论：缺氧后给予LEV可减少神经细胞的凋亡。因此，我们认为LEV作为一种有效的抗癫痫和抗凋亡药物，可能是控制HIBI新生儿癫痫发作活动的一种可行的选择。(C)2012爱思唯尔爱尔兰有限公司。保留所有权利。
Background: Hypoxic-ischemic brain injury (HIBI) is a common cause of neonatal mortality and morbidity. The use of levetiracetam (LEV), as a potential neuroprotective in brain ischemia, receives an increasingly high attention, and it could have a crucial role in the regulation of epileptogenesis and neuroprotection. Potential effects of LEV on neuronal apoptosis in HIBI have not previously been reported in literature.Objectives: The aim of this study is to evaluate the possible effects of LEV on neuronal apoptosis in neonatal rat model of HIBI.Methods: Seven-day-old Wistar rat pups were subjected to right common carotid artery ligation and hypoxia (92% nitrogen and 8% oxygen) for 2 h. The pups were treated with LEV or saline after hypoxia. In sham group rats, neither ligation, nor hypoxia was performed. Neuronal apoptosis was evaluated by the terminal deoxynucleotidyltransferase- mediated dUTP nick-end labeling (TUNEL) methods.Results: The counts of apoptotic cells in both hippocampus and cerebral cortex were significantly higher in the saline treatment group than in the sham group. The counts of apoptotic cells in both hippocampus and cerebral cortex were similar to those in the sham group and in the LEV treatment group. The number of apoptotic cells decreased significantly in the LEV-treated group compared with the saline group.Conclusions: These results show that LEV administration after hypoxia reduces neuronal apoptosis. Thus, we propose that LEV, as an effective antiepileptic and antiapoptotic drug, may be a viable choice for the control of seizure activity in neonates with HIBI. (C) 2012 Elsevier Ireland Ltd. All rights reserved.