Jafarian M, Karimzadeh F, Alipour F, Attari F, Lotfinia A A, Speckmann E-J, Zarrindast M-R, Gorji A
School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran; Shefa Neuroscience Research Centre, Khatam Alanbia Hospital, Tehran, Iran.
Shefa Neuroscience Research Centre, Khatam Alanbia Hospital, Tehran, Iran.
Neuroscience. 2015 Jul 9;298:161-70. doi: 10.1016/j.neuroscience.2015.04.033. Epub 2015 Apr 20.
Growing numbers of evidence indicate that cognitive impairments are part of clinical profile of childhood absence epilepsy. Little is known on neuropathological changes accompanied by cognitive deficits in absence epilepsy. The aim of the present study was to investigate age-dependent neuropathological changes accompanied by learning and memory impairments in Wistar Albino Glaxo from Rijswijk (WAG/Rij) rat model of absence epilepsy. Experimental groups were divided into four groups of six rats of both WAG/Rij and Wistar strains with 2 and 6 months of age. The learning and memory performances were assessed using passive avoidance paradigm and neuropathological alterations were investigated by the evaluation of the number of dark neurons and apoptotic cells as well as the expression of caspase-3 in the neocortex, the hippocampus, and different regions of the thalamus. Results revealed a decline in learning and spatial memory of 6-month-old WAG/Rij rats compared to age-matched Wistar rats as well as 2-month-old WAG/Rij and Wistar rats. The mean number of dark neurons was significantly higher in the hippocampal CA1 and CA3 areas as well as in the laterodorsal, centromedial, and reticular thalamic nuclei and the somatosensory cortex of 6-month-old WAG/Rij rats. In addition, a higher number of apoptotic cells as well as a higher expression of caspase-3 was observed in the hippocampal CA1 and CA3 regions, the laterodorsal thalamic nucleus, and the somatosensory cortex of 6-month-old WAG/Rij rats compared to other animal groups. These results indicate significant enhancement of neuronal damage and cell death accompanied by memory deficits after seizure attacks in a rat model of absence epilepsy. Seizure-induced neuronal injury and death may underlie cognitive impairments in absence epilepsy.
越来越多的证据表明，认知障碍是儿童失神癫痫临床特征的一部分。关于失神癫痫中伴随认知缺陷的神经病理学变化，人们所知甚少。本研究的目的是在里耶斯维克白化Wistar大鼠（WAG/Rij）失神癫痫模型中，研究与学习和记忆障碍相关的年龄依赖性神经病理学变化。实验组分为四组，每组六只WAG/Rij和Wistar品系的大鼠，年龄分别为2个月和6个月。使用被动回避范式评估学习和记忆表现，并通过评估新皮层、海马体和丘脑不同区域的暗神经元数量、凋亡细胞数量以及caspase-3的表达来研究神经病理学改变。结果显示，与年龄匹配的Wistar大鼠以及2个月大的WAG/Rij和Wistar大鼠相比，6个月大的WAG/Rij大鼠的学习和空间记忆能力下降。6个月大的WAG/Rij大鼠海马体CA1和CA3区域、丘脑后外侧核、丘脑中央内侧核、丘脑网状核以及体感皮层的暗神经元平均数量显著更高。此外，与其他动物组相比，6个月大的WAG/Rij大鼠海马体CA1和CA3区域、丘脑后外侧核以及体感皮层的凋亡细胞数量更多，caspase-3的表达也更高。这些结果表明，在失神癫痫大鼠模型中，癫痫发作后神经元损伤和细胞死亡显著增加，并伴有记忆缺陷。癫痫发作诱导的神经元损伤和死亡可能是失神癫痫认知障碍的基础。
