Rutten Annemarieke, van Albada Mirjam, Silveira Diosely C, Cha Byung Ho, Liu Xianzeng, Hu Yingchu N, Cilio Maria Roberta, Holmes Gregory L
Department of Neurology, Harvard Medical School, Children's Hospital, Boston, MA 02115, USA.
Eur J Neurosci. 2002 Aug;16(3):501-13. doi: 10.1046/j.1460-9568.2002.02103.x.
Status epilepticus (SE) has a high mortality and morbidity rate in children. Disturbances in learning and memory are frequently associated with SE although it is not clear when the cognitive deficits occur. If cognitive dysfunction occurs immediately following the seizure, the window of opportunity for therapeutic intervention is limited. The first goal of this study was to determine the timing of cognitive dysfunction following SE in weanling rats. As there is evidence that enriching the environment can improve cognitive and motor deficits following brain injury, our second goal was to determine whether environmental enrichment improves cognitive function following SE. Rats underwent lithium-pilocarpine-induced SE at postnatal (P) day 20 and were then tested for visual-spatial memory in the water maze at P22, P25, P30, or P50. Rats with SE performed significantly worse in the water maze than control rats at all time points. Once the time-courses of visual-spatial memory deficits were determined, a second group of P20 rats were subjected to SE and were then placed in an enriched environment (enriched group) or remained in standard cages in the vivarium (nonenriched group) for 28 days. Following environmental manipulation, the animals were tested in the water maze. Rats housed in an enriched environment following the SE performed substantially better in the water maze than rats housed in standard cages. However, no differences were found between the enriched and nonenriched groups in EEG or histological evaluation. Although SE results in cognitive impairment within days of the seizure, housing in an enriched environment after SE has a beneficial effect on cognitive performance in rats.
癫痫持续状态(SE)在儿童中具有较高的死亡率和发病率。尽管尚不清楚认知缺陷何时出现,但学习和记忆障碍常与SE相关。如果在癫痫发作后立即出现认知功能障碍,治疗干预的机会窗口就会受限。本研究的首要目标是确定幼龄大鼠SE后认知功能障碍的发生时间。由于有证据表明丰富环境可改善脑损伤后的认知和运动缺陷,我们的第二个目标是确定环境丰富化是否能改善SE后的认知功能。大鼠在出生后(P)第20天接受锂-匹罗卡品诱导的SE,然后在P22、P25、P30或P50时在水迷宫中测试视觉空间记忆。在所有时间点,SE大鼠在水迷宫中的表现均显著差于对照大鼠。一旦确定了视觉空间记忆缺陷的时间进程,第二组P20大鼠接受SE,然后置于丰富环境中(丰富组)或留在动物饲养室的标准笼中(非丰富组)28天。在环境处理后,对动物进行水迷宫测试。SE后饲养在丰富环境中的大鼠在水迷宫中的表现明显优于饲养在标准笼中的大鼠。然而,在脑电图或组织学评估中,丰富组和非丰富组之间未发现差异。尽管SE在癫痫发作数天内会导致认知障碍,但SE后饲养在丰富环境中对大鼠的认知表现有有益影响。