中国神经再生研究(英文版) ›› 2014, Vol. 9 ›› Issue (5): 526-533.doi: 10.4103/1673-5374.130083

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

颞叶癫痫者脑组织中Notch1表达增加:动物模型和临床证据

  

  • 收稿日期:2014-02-25 出版日期:2014-03-12 发布日期:2014-03-12
  • 基金资助:

    湖北省子自然科学基金项目(02.02.040458)

Increased expression of Notch1 in temporal lobe epilepsy: animal models and clinical evidence

Xijin Liu, Zhiyong Yang, Yaping Yin, Xuejun Deng   

  1. Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China
  • Received:2014-02-25 Online:2014-03-12 Published:2014-03-12
  • Contact: Xuejun Deng, M.D., Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China, dengxuejun1965@sina.com.
  • Supported by:

    This study was funded by the Natural Science Foundation of Hubei Province in China, No. 02.02.040458.

摘要:

实验使用免疫组化方法检测了颞叶组织注射毛果芸香碱诱导癫痫大鼠脑组织中Notch1,Hes1和胶质纤维酸性蛋白的表达及顽固性颞叶癫痫患者颞叶皮质组织中Notch1和Hes1的表达。结果发现癫痫持续状态和自发反复癫痫发作大鼠脑组织中Notch1,Hes1和胶质纤维酸性蛋白的表达增加,而经过Notch1阻滞剂苯噻羟脲干预的自发反复发作大鼠皮质和海马中Notch1,Hes1和胶质纤维酸性蛋白的表达均未出现明显变化。临床观察也证实,与无颞叶癫痫者相比,顽固性颞叶癫痫患者颞叶中Notch1和Hes1表达增加。提示Notch1可能在颞叶癫痫的发病中发挥重要作用,苯噻羟脲发挥对Notch1信号通路的阻滞作用,可能成为治疗颞叶癫痫的一种新方法。

关键词: 神经再生, 脑损伤, 癫痫, 颞叶癫痫, 星形胶质细胞增生, Notch1, Hes1, 胶质纤维酸性蛋白, 氯化锂-匹罗卡品, 苯噻羟脲, 基金资助文章

Abstract:

Temporal lobe epilepsy is associated with astrogliosis. Notch1 signaling can induce astrogliosis in glioma. However, it remains unknown whether Notch1 signaling is involved in the pathogenesis of epilepsy. This study investigated the presence of Notch1, hairy and enhancer of split-1, and glial fibrillary acidic protein in the temporal neocortex and hippocampus of lithium-pilocarpine-treated rats. The presence of Notch1 and hairy and enhancer of split-1 was also explored in brain tissues of patients with intractable temporal lobe epilepsy. Quantitative electroencephalogram analysis and behavioral observations were used as auxiliary measures. Results revealed that the presence of Notch1, hairy and enhancer of split-1, and glial fibrillary acidic protein were enhanced in status epilepticus and vehicle-treated spontaneous recurrent seizures rats, but remain unchanged in the following groups: control, absence of either status epilepticus or spontaneous recurrent seizures, and zileuton-treated spontaneous recurrent seizures. Compared with patient control cases, the presences of Notch1 and hairy and enhancer of split-1 were upregulated in the temporal neocortex of patients with intractable temporal lobe epilepsy. Therefore, these results suggest that Notch1 signaling may play an important role in the onset of temporal lobe epilepsy via astrogliosis. Furthermore, zileuton may be a potential therapeutic strategy for temporal lobe epilepsy by blocking Notch1 signaling.

Key words: nerve regeneration, brain injury, epilepsy, temporal lobe epilepsy, astrogliosis, Notch1, hairy and enhancer of split-1, glial fibrillary acidic protein, LiCl-pilocarpine, zileuton, the Natural Science Foundation of Hubei Province, neural regeneration