Yin Ping, Zhang Xin-Ting, Li Jun, Yu Lin, Wang Ji-Wen, Lei Ge-Fei, Sun Ruo-Peng, Li Bao-Min
Pediatric Department of Qilu Hospital, Shandong University, Jinan, China; Brain Science Research Institute, Shandong University, Jinan, China.
Women's Hospital, School of Medicine, Zhejiang University, China.
Epilepsy Behav. 2015 Jun;47:93-7. doi: 10.1016/j.yebeh.2015.04.018. Epub 2015 May 14.
Epidemiological data suggest a relationship between maternal infection and a high incidence of childhood epilepsy in offspring. However, there is little experimental evidence that links maternal infection with later seizure susceptibility in juvenile offspring. Here, we asked whether maternal immune challenge during pregnancy can alter seizure susceptibility and seizure-associated brain damage in adolescence. Pregnant Sprague-Dawley rats were treated with lipopolysaccharide (LPS) or normal saline (NS) on gestational days 15 and 16. At postnatal day 21, seizure susceptibility to kainic acid (KA) was evaluated in male offspring. Four groups were studied, including normal control (NS-NS), prenatal infection (LPS-NS), juvenile seizure (NS-KA), and "two-hit" (LPS-KA) groups. Our results demonstrated that maternal LPS exposure caused long-term reactive astrogliosis and increased seizure susceptibility in juvenile rat offspring. Compared to the juvenile seizure group, animals in the "two-hit" group showed exaggerated astrogliosis, followed by worsened spatial learning ability in adulthood. In addition, prenatal immune challenge alone led to spatial learning impairment in offspring but had no effect on anxiety. These data suggest that prenatal immune challenge causes a long-term increase in juvenile seizure susceptibility and exacerbates seizure-induced brain injury, possibly by priming astroglia.
流行病学数据表明，母体感染与后代儿童期癫痫的高发病率之间存在关联。然而，几乎没有实验证据表明母体感染与幼年后代日后的癫痫易感性有关。在此，我们探究了孕期母体免疫应激是否会改变青春期的癫痫易感性和癫痫相关脑损伤。在妊娠第15天和第16天，对怀孕的斯普拉格-道利大鼠给予脂多糖（LPS）或生理盐水（NS）处理。在出生后第21天，评估雄性后代对 kainic 酸（KA）的癫痫易感性。研究了四组，包括正常对照（NS-NS）、产前感染（LPS-NS）、幼年癫痫（NS-KA）和“双打击”（LPS-KA）组。我们的结果表明，母体暴露于LPS会导致幼年大鼠后代长期的反应性星形胶质细胞增生，并增加癫痫易感性。与幼年癫痫组相比，“双打击”组的动物表现出更严重的星形胶质细胞增生，随后成年期的空间学习能力恶化。此外，单独的产前免疫应激会导致后代空间学习障碍，但对焦虑没有影响。这些数据表明，产前免疫应激会导致幼年癫痫易感性长期增加，并加剧癫痫诱导的脑损伤，可能是通过使星形胶质细胞致敏来实现的。
