Sutula T, Lauersdorf S, Lynch M, Jurgella C, Woodard A
Department of Neurology, University of Wisconsin, Madison 53792, USA.
J Neurosci. 1995 Dec;15(12):8295-301. doi: 10.1523/JNEUROSCI.15-12-08295.1995.
Repeated activation of neural pathways by kindling induces brief seizures, permanent increases in seizure susceptibility, neuronal loss in the hippocampus, and mossy fiber sprouting in the dentate gyrus. Because kindling induces permanent cellular alterations in hippocampal pathways that have been implicated in memory, it was of interest to determine if kindling also induces long-lasting impairments in a spatial memory task in rats. In this study, the effects of kindling on memory were investigated by assessing kindled rats in a radial arm maze behavior that is impaired by hippocampal damage. Kindled rats studied at 1 month after the last of 30-134 evoked generalized tonic-clonic seizures acquired competence in the performance of the radial arm maze task at a rate that was indistinguishable from age-matched normal controls, but demonstrated a deficit in the ability to repeat the task on consecutive days. The repetition deficit was not observed in rats that experienced three afterdischarges or three generalized tonic-clonic seizures, and the severity of the deficit varied directly with the number of evoked kindled seizures. Repeated brief seizures evoked by kindling induced a long-lasting deficit in a radial arm maze task that is a rodent model of memory. The observation of a long-lasting deficit in radial arm maze performance in kindled rats suggests that the cellular alterations induced in the hippocampus by seizures could contribute to the memory dysfunction in human epilepsy.
通过点燃反复激活神经通路会诱发短暂性癫痫发作、癫痫易感性的永久性增加、海马体中的神经元丢失以及齿状回中的苔藓纤维发芽。由于点燃会在与记忆相关的海马体通路中诱发永久性细胞改变，因此确定点燃是否也会在大鼠的空间记忆任务中导致长期损伤就变得很有意义。在本研究中，通过在因海马体损伤而受损的放射状臂迷宫行为中评估点燃大鼠，来研究点燃对记忆的影响。在诱发30 - 134次全身性强直阵挛性癫痫发作中的最后一次发作后1个月进行研究的点燃大鼠，在放射状臂迷宫任务的表现上获得能力的速度与年龄匹配的正常对照组没有区别，但在连续几天重复该任务的能力上表现出缺陷。在经历三次后放电或三次全身性强直阵挛性癫痫发作的大鼠中未观察到重复缺陷，并且缺陷的严重程度与诱发的点燃癫痫发作次数直接相关。通过点燃诱发的反复短暂性癫痫发作在作为记忆啮齿动物模型的放射状臂迷宫任务中导致了长期缺陷。在点燃大鼠中观察到放射状臂迷宫表现的长期缺陷表明，癫痫发作在海马体中诱发的细胞改变可能导致人类癫痫中的记忆功能障碍。
