噻哌啶对戊四氮点燃癫痫大鼠癫痫发作发展和记忆障碍的影响。

Effects of thioperamide on seizure development and memory impairment induced by pentylenetetrazole-kindling epilepsy in rats.

机构信息

Department of Neurology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310016, China.

出版信息

Chin Med J (Engl). 2013 Jan;126(1):95-100.

PMID:23286485

Abstract

BACKGROUND

Histamine H(3) receptor antagonists have been considered as potential drugs to treat central nervous system diseases. However, whether these drugs can inhibit epileptogenesis remains unclear. This study aimed to investigate the effects of thioperamide, a selective and potent histamine H(3) receptor antagonist, on the seizure development and memory impairment induced by pentylenetetrazole (PTZ)-kindling epilepsy in rats.

METHODS

Chemical kindling was elicited by repeated intraperitoneal (ip) injections of a subconvulsant dose of PTZ (35 mg/kg) once every 48 hours for 12 times, and seizure activity of kindling was recorded for 30 minutes. Control rats were ip injected with saline instead of PTZ. Morris water maze was used to evaluate the spatial memory. Phosphorylated cyclic adenosine monophosphate response element binding protein (p-CREB) was tested by Western blotting in hippocampus.

RESULTS

Intracerebroventricular (icv) injections with thioperamide (10 µg, 20 µg) 30 minutes before every PTZ injections, significantly prolonged the onset of PTZ-kindling and inhibited the seizure stages. PTZ-kindling seizures led to the impairment of spatial memory in rats, and thioperamide ameliorated the impairment of spatial learning and memory. Compared to non-kindling rats, there was a significant decrease in p-CREB level in hippocampus of the PTZ-kindling rats, which was reversed by thioperamide.

CONCLUSIONS

Thioperamide plays a protective role in seizure development and cognitive impairment of PTZ-induced kindling in rats. The protection of thioperamide in cognitive impairment is possibly associated with the enhancement of CREB-dependent transcription.

摘要

背景

组胺 H（3）受体拮抗剂已被认为是治疗中枢神经系统疾病的潜在药物。然而，这些药物是否能抑制癫痫发作仍不清楚。本研究旨在探讨噻哌酰胺（一种选择性和强效的组胺 H（3）受体拮抗剂）对戊四氮（PTZ）点燃癫痫大鼠癫痫发作发展和记忆损伤的影响。

方法

通过重复腹腔（ip）注射亚惊厥剂量的 PTZ（35mg/kg），每 48 小时一次，共 12 次，诱发化学点燃，记录点燃发作 30 分钟。对照大鼠用生理盐水代替 PTZ 腹腔注射。Morris 水迷宫用于评估空间记忆。通过 Western blot 检测海马磷酸化环腺苷酸反应元件结合蛋白（p-CREB）。