Neurobiology Program, Ann & Robert H. Lurie Children's Hospital of Chicago Research Center, Department of Pediatrics, Northwestern University, Feinberg School of Medicine, Chicago, IL 60614, USA.
Epilepsy Behav. 2013 Oct;29(1):190-7. doi: 10.1016/j.yebeh.2013.07.018. Epub 2013 Aug 23.
Prolonged early-life seizures are associated with disruptions of affective and cognitive function. Postictal disturbances, temporary functional deficits that persist for hours to days after seizures, have not yet been thoroughly characterized. Here, we used kainic acid (KA) to induce status epilepticus (SE) in immature rats at three developmental stages (postnatal day (P) 15, 21, or 30) and subsequently assessed spatial learning and memory in a Barnes maze, exploratory behavior in an open field, and the spatiotemporal distribution of cell injury during the first 7-10 days of the postictal period. At 1 day post-SE, P15-SE rats showed no deficit in the Barnes maze but were hyperexploratory in an open field compared with their littermate controls. In contrast, P21- and P30-SE rats exhibited markedly impaired performance in the Barnes maze and exhibited significantly reduced open field exploration suggestive of anxiety-like behavior. These behavioral changes were transient in P15 rats but more persistent in P21 and enduring in P30 rats after KA-SE. The time course of behavioral deficits in P21 and P30 rats was temporally correlated with the presence of neuronal injury in the lateral septal nuclei, amygdala, and ventral subiculum/CA1, regions involved in modulation of the hypothalamic-pituitary-adrenal stress response.
早期生命中长时间的癫痫发作与情感和认知功能的紊乱有关。发作后障碍(postictal disturbances),即发作后持续数小时到数天的暂时功能缺陷,尚未得到彻底描述。在这里,我们使用海人酸(kainic acid, KA)在三个发育阶段(出生后第 15 天、21 天或 30 天)诱导未成熟大鼠的癫痫持续状态(status epilepticus, SE),并随后在巴恩斯迷宫中评估空间学习和记忆、在开阔场中评估探索行为,以及在发作后第 1 天到第 7 天到第 10 天期间评估细胞损伤的时空分布。在 SE 后 1 天,P15-SE 大鼠在巴恩斯迷宫中没有表现出缺陷,但与同窝对照相比,在开阔场中表现出过度探索行为。相比之下,P21-SE 和 P30-SE 大鼠在巴恩斯迷宫中的表现明显受损,在开阔场中的探索明显减少,提示存在焦虑样行为。这些行为变化在 P15 大鼠中是短暂的,但在 P21 大鼠中更为持久,在 P30 大鼠中则是持久的。P21 和 P30 大鼠的行为缺陷的时间进程与外侧隔核、杏仁核和腹侧 subiculum/CA1 中的神经元损伤存在时间相关性,这些区域参与调节下丘脑-垂体-肾上腺应激反应。