Pediatric Department of Qilu Hospital, Shandong University, Jinan, China.
Epilepsy Behav. 2013 Apr;27(1):9-17. doi: 10.1016/j.yebeh.2012.12.015. Epub 2013 Jan 24.
Our aim was to examine whether neonatal lipopolysaccharide (LPS) exposure is associated with changes in microglia and whether these alternations could influence later seizure-induced neurobehavioral outcomes. Male pups were first injected intraperitoneally with either LPS or saline on postnatal day 3 (P3) and postnatal day 5 (P5). Immunohistochemical analysis showed that LPS-treated animals exhibited increased microglia activation that persisted into adolescence. At P45, seizures were induced in rats by intraperitoneal injection of kainic acid (KA). Rats treated with LPS neonatally showed significantly greater proinflammatory responses and performed significantly worse in the Y-maze, Morris water maze, and inhibitory avoidance tasks after KA insult. Treatment with minocycline at the time of neonatal LPS exposure to block LPS-induced microglia alternation attenuated the exaggerated neuroinflammatory responses and alleviated memory impairment associated with the KA insult. Our findings suggest that neonatal immune activation can predispose the brain to exacerbated behavioral deficits following seizures in adulthood, possibly by priming microglia.
我们的目的是研究新生儿脂多糖（LPS）暴露是否与小胶质细胞的变化有关，以及这些变化是否会影响随后的癫痫诱导的神经行为结果。雄性幼崽首先在出生后第 3 天（P3）和第 5 天（P5）腹膜内注射 LPS 或生理盐水。免疫组织化学分析显示，LPS 处理的动物表现出小胶质细胞激活增加，这种激活持续到青春期。在 P45，通过腹膜内注射海人酸（KA）诱导大鼠癫痫发作。在 KA 损伤后，新生期接受 LPS 处理的大鼠表现出明显更强的促炎反应，在 Y 迷宫、莫里斯水迷宫和抑制性回避任务中的表现明显更差。在新生 LPS 暴露时用米诺环素治疗以阻断 LPS 诱导的小胶质细胞改变，减轻了与 KA 损伤相关的过度神经炎症反应和记忆障碍。我们的研究结果表明，新生儿免疫激活可使大脑在成年后癫痫发作后更容易出现行为缺陷，可能是通过启动小胶质细胞。
