EPILEPTIC NEURONAL ACTIVITY AND HIPPOCAMPAL DAMAGE

已开发了一个实验模型来研究功能 和癫痫发作活动的结构后果，并阐明 海马体的正常结构和功能。癫痫发作 海马体的活动，这发生在人类的颞叶 癫痫，最常见的癫痫形式，处于 癫痫是一种持续的癫痫放电状态，通常 与海马区损伤的特征模式有关。 这种损伤模式可以在正常动物身上复制，方法是 电刺激穿支通路，主要传入 通向海马体的路径。被刺激并被允许的动物 可以使用不同时间段的恢复来确定更改 在功能和结构上是癫痫发作的结果 活动。因此，这些动物构成了一个方面的模型 癫痫状态的影响，即反复发作的影响。 已经设计了实验来确定两者之间的关系 在选择性神经元丢失和观察到的 剩余神经元的兴奋性和抑制性控制。 首先使用退化方法来准确地确定 神经元因癫痫发作活动而受到不可逆转的损害。这些细胞 最敏感的将被确定为他们的位置 传出的投影。然后，使用免疫细胞化学方法。 以确定可能被消耗的神经活性物质 癫痫引起的敏感神经元和中间神经元的丢失。 由于抑制作用的长期下降已被发现 由刺激诱发癫痫所致，这些细胞可能 将确定对这一功能赤字负有责任的人。他们 将以不涉及癫痫发作的方式移除，以便 确定哪些中间神经元在不可逆转地受损时可能是 对癫痫发作后发生的变化负责。长的- 这项研究的术语目标是描述有害影响 癫痫本身的活动，并确定其机制 癫痫发作会造成不可逆转的损害。这将允许 制定预防癫痫脑损伤的策略并 延缓了这种疾病可能的进行性。

An experimental model has been developed to study the functional and structural consequences of seizure activity and to elucidate the normal structure and function of the hippocampus. Seizure activity in the hippocampus, which occurs in human temporal lobe epilepsy, the most common form of epilepsy, and in status epilepticus, a condition of continuous seizure discharge, is often associated with a characteristic pattern of hippocampal damage. This pattern of damage can be replicated in normal animals by electrical stimulation of the perforant path, the main afferent pathway to the hippocampus. Animals stimulated and allowed to recover for various periods can be used to determine the changes in function and structure that occur as a result of seizure activity. These animals therefore constitute a model of one aspect of the epileptic state, ie, the effects of repetitive seizures. Experiments have been designed to determine the relationship between selective neuron loss and the observed changes in both the excitability and inhibitory control of remaining neurons. Degeneration methods are used first to determine precisely which neurons are irreversibly damaged by seizure activity. The cells most sensitive will be identified as will the location of their efferent projections. Then, immunocytochemical methods are used to identify the neuroactive substances that may be depleted by the seizure-induced loss of susceptible neurons and interneurons. Since a long-lasting decrease in inhibition has been found to result from stimulation-induced seizures, the cells possibly responsible for this functional deficit will be identified. They will then be removed by means not involving seizures in order to determine which interneurons, when irreversibly damaged, might be responsible for the changes that occur after seizures. The long- term goals of this research are to describe the detrimental effects of seizure activity per se and to determine the mechanism by which seizures cause irreversible damage. This will allow the development of strategies to prevent epileptic brain damage and to retard the possibly progressive nature of the disorder.