Department of Neurology, Neuroscience Center at Dartmouth, Dartmouth Medical School, Hanover, New Hampshire 03756, USA.
Neurobiol Dis. 2010 Sep;39(3):362-71. doi: 10.1016/j.nbd.2010.05.002. Epub 2010 May 7.
Frequent interictal spikes are a common finding in the electroencephalograms of children with epileptic encephalopathies. While it is well recognized that interictal spikes are a biological marker of seizures and can lead to transitory cognitive impairment, whether interictal spikes can result in long-standing adverse effects on learning and memory in children is not known. Here we investigated the consequences of interictal spikes in rat pups without seizures on long-term learning and memory. Rat pups were given a low dose of flurothyl for 4h for 10 days during continuous electroencephalographic monitoring. Rats developed interictal spikes without seizures while age-matched controls under similar testing conditions had few interictal spikes. When rats were tested as adults, there was impairment in reference memory in the probe test of the Morris water maze, reference memory impairment in the four-trial radial-arm water maze and impaired long-term potentiation. Early-life interictal spikes resulted in impaired new cell formation and decreased cell counts in the hippocampus but did not cause an increase in apoptosis. This study, for the first time demonstrates that interictal spikes in rat pups without seizures can result in long-standing spatial cognitive impairment. Our findings suggest that suppressing IIS may be as important as treating seizures during brain development.
癫痫性脑病患儿的脑电图常出现阵发性尖波。阵发性尖波是癫痫发作的生物学标志物,可导致短暂性认知障碍,但阵发性尖波是否会对儿童的学习和记忆产生长期不良影响尚不清楚。在此,我们研究了无癫痫发作的幼鼠阵发性尖波对长期学习和记忆的影响。在连续脑电图监测下,幼鼠连续 10 天接受低剂量氟烷处理 4 小时。与在类似测试条件下仅有少量阵发性尖波的同龄对照鼠相比,接受处理的鼠出现了阵发性尖波而无癫痫发作。当这些鼠成年后,在 Morris 水迷宫的探针测试中出现参考记忆障碍,在四臂水迷宫的参考记忆障碍和长时程增强受损。生命早期的阵发性尖波导致海马中新细胞形成受损和细胞计数减少,但不会导致细胞凋亡增加。本研究首次证明,无癫痫发作的幼鼠阵发性尖波可导致长期的空间认知障碍。我们的研究结果表明,在大脑发育过程中,抑制阵发性尖波可能与治疗癫痫同等重要。