Stover Kurt R, Lim Stellar, Zhou Terri-Lin, Stafford Paul M, Chow Jonathan, Li Haoyuan, Sivanenthiran Nila, Mylvaganam Sivakami, Wu Chiping, Weaver Donald F, Eubanks James, Zhang Liang
Krembil Research Institute, University Health Network, Canada.
Departments of Chemistry, University of Toronto, Canada.
IBRO Rep. 2017 Sep 24;3:33-44. doi: 10.1016/j.ibror.2017.08.001. eCollection 2017 Dec.
The incidence of seizures increases with old age. Stroke, dementia and brain tumors are recognized risk factors for new-onset seizures in the aging populations and the incidence of these conditions also increased with age. Whether aging is associated with higher seizure susceptibility in the absence of the above pathologies remains unclear. We used classic kindling to explore this issue as the kindling model is highly reproducible and allows close monitoring of electrographic and motor seizure activities in individual animals. We kindled male young and aging mice (C57BL/6 strain, 2-3 and 18-22 months of age) via daily hippocampal CA3 stimulation and monitored seizure activity via video and electroencephalographic recordings. The aging mice needed fewer stimuli to evoke stage-5 motor seizures and exhibited longer hippocampal afterdischarges and more frequent hippocampal spikes relative to the young mice, but afterdischarge thresholds and cumulative afterdischarge durations to stage 5 motor seizures were not different between the two age groups. While hippocampal injury and structural alterations at cellular and micro-circuitry levels remain to be examined in the kindled mice, our present observations suggest that susceptibility to hippocampal CA3 kindling seizures is increased with aging in male C57 black mice.
癫痫发作的发生率随年龄增长而增加。中风、痴呆和脑肿瘤是老年人群新发癫痫的公认危险因素,且这些疾病的发生率也随年龄增长而上升。在没有上述病理状况的情况下,衰老是否与更高的癫痫易感性相关仍不清楚。我们使用经典的点燃模型来探讨这个问题,因为点燃模型具有高度可重复性,并且可以密切监测个体动物的脑电图和运动性癫痫活动。我们通过每日海马CA3刺激对雄性年轻和老年小鼠(C57BL/6品系,2 - 3个月和18 - 22个月大)进行点燃,并通过视频和脑电图记录监测癫痫活动。相对于年轻小鼠,老年小鼠诱发5期运动性癫痫所需的刺激更少,海马后放电时间更长,海马棘波更频繁,但两个年龄组之间5期运动性癫痫的后放电阈值和累积后放电持续时间并无差异。虽然在点燃小鼠中,海马损伤以及细胞和微电路水平的结构改变仍有待研究,但我们目前的观察结果表明,雄性C57黑小鼠对海马CA3点燃癫痫的易感性随衰老而增加。