Yang Lu, Li Fuhai, Zhang Haiju, Ge Wei, Mi Changrui, Sun Ruopeng, Liu Chunxi
Department of Pediatrics, Qilu Hospital, Shandong University, Jinan, Shandong Province 250012, China.
Epilepsy Res. 2009 Oct;86(2-3):209-20. doi: 10.1016/j.eplepsyres.2009.07.001. Epub 2009 Jul 29.
Frequently repetitive febrile seizures (FRFS) in immature brain could impair long-term memory without obvious pathological alteration. Although astrocyte activation has been implicated in many seizure models, it has never been examined in febrile seizure models. We investigated astrocyte activation states after FRFS in postnatal-10-day (P10) rats by western blot and immunohistochemical analysis of GFAP and S100beta, two protein markers for activated astrocytes, at three time points (P25, P35, P45). The levels of GFAP and S100beta increased significantly at all the time examined. Furthermore, we administered propentofylline, an astrocyte modulator, to verify the relationship between the activated astrocytes and memory injury. After propentofylline treatment for 10 consecutive days following P10 frequently repetitive FS, rats exhibited improved performances in Morris water maze at P36 and inhibitory avoidance task at P45, along with markedly suppressed overexpression of GFAP and S100beta. This research suggests that modulation of astrocyte activation might be a potential therapeutic target to improve memory outcomes after frequently repetitive febrile seizures.
幼龄大脑中频繁发作的热性惊厥(FRFS)可能会损害长期记忆,且无明显病理改变。尽管星形胶质细胞激活在许多癫痫模型中都有涉及,但在热性惊厥模型中从未进行过研究。我们通过蛋白质免疫印迹法以及对GFAP和S100β(两种活化星形胶质细胞的蛋白质标志物)进行免疫组化分析,在三个时间点(P25、P35、P45)研究了出生后10天(P10)大鼠发生FRFS后的星形胶质细胞激活状态。在所检测的所有时间点,GFAP和S100β的水平均显著升高。此外,我们给予星形胶质细胞调节剂丙戊茶碱,以验证活化星形胶质细胞与记忆损伤之间的关系。在P10频繁发作热性惊厥后连续10天给予丙戊茶碱治疗,大鼠在P36时的莫里斯水迷宫实验以及在P45时的抑制性回避任务中表现均有所改善,同时GFAP和S100β的过表达明显受到抑制。本研究表明,调节星形胶质细胞激活可能是改善频繁发作热性惊厥后记忆结果的一个潜在治疗靶点。