中国神经再生研究(英文版) ›› 2015, Vol. 10 ›› Issue (4): 599-604.doi: 10.4103/1673-5374.155434

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

短期使用抗癫痫药物对未成熟大脑神经元也有损害

  

  • 收稿日期:2015-03-21 出版日期:2015-04-22 发布日期:2015-04-22
  • 基金资助:

    国家自然科学基金项目(30973224)西安交通大学第二附属医院人才培养项目(RC(XM)200908),陕西省重点科技项目(2006k15-G1(2))

Short-term use of antiepileptic drugs is neurotoxic to the immature brain

Yu Liu, Xue-ying Wang, Dan Li, Lin Yang, Shao-ping Huang   

  1. Department of Pediatrics, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi Province, China
  • Received:2015-03-21 Online:2015-04-22 Published:2015-04-22
  • Contact: Lin Yang, M.D., yr_1217@163.com
  • Supported by:

    This study was financially supported by grants from the National Natural Science Foundation of China, No. 30973224; Talent Cultivation Funds of the Second Affiliated Hospital of Xi’an Jiaotong University of China, No. RC(XM)200908; a grant from the Key Science and Technology Project of Shaanxi Province of China, No. 2006k15-G1(2).

摘要:

既往研究显示长期使用抗癫痫药物会对神经系统产生损害,然而对于婴幼儿,特别是新生儿,使用抗癫痫药物的时间通常比较短,这种情况是否也会损伤大脑神经元呢?实验对出生3-21d的未成熟大鼠连续3d腹腔注射苯巴比妥和/或托吡酯。HE染色和免疫组化染色结果发现苯巴比妥和/或托吡酯对未成熟大鼠大脑海马CA1区神经元产生了损伤,且抑制大鼠大脑海马CA1区兴奋性氨基酸受体亚单位GluR1和NR2B的表达,两种药物联用的损伤效果大于单独使用一种药物。说明短期使用抗癫痫药物也会损害未成熟大脑神经元,2种药物联用的破坏作用大于单独一种药物,因此作者建议临床应用时应更谨慎使用抗癫痫药物的联合应用。

关键词: 神经再生, 癫痫, 抗癫痫药, 未成熟大脑, 海马, 突触可塑性, 谷氨酸受体

Abstract:

Previous studies have shown that the long-term use of antiepileptic drugs can cause nervous system damage. However, short-term antiepileptic drug treatment is frequently given to infants, especially neonates, to control seizure. Whether the short-term use of antiepileptic drugs is neurotoxic remains unclear. In the present study, immature rats, 3–21 days of age, were intraperitoneally injected with phenobarbital and/or topiramate for 3 consecutive days. Hematoxylin-eosin and immunohistochemical staining revealed that phenobarbital and topiramate, individually or in combination, were cytotoxic to hippocampal CA1 neurons and inhibited the expression of GluR1 and NR2B, excitatory glutamate receptor subunits. Furthermore, the combination of the two drugs caused greater damage than either drug alone. The results demonstrate that the short-term use of antiepileptic drugs damages neurons in the immature brain and that the combined use of antiepileptic drugs exacerbates damage. Our findings suggest that clinicians should consider the potential neurotoxic risk associated with the combined use of antiepileptic drugs in the treatment of seizure.

Key words: nerve regeneration, seizure, antiepileptic drugs, immature brain, hippocampus, synaptic plasticity, glutamate receptor, NSFC grant, neural regeneration