HIPPOCAMPAL DAMAGE AS A CAUSE OF EPILEPSY

海马细胞丢失的几种模式被观察到， 颞叶起源局灶性癫痫的临床人群。 它 普遍认为，缉获量， 缺血性/缺氧性窘迫早于海马损伤。 然而，一旦生产出来， 这种细胞损伤是否会导致癫痫的发展 的 本建议检查急性和慢性生理， 形态学和神经化学的后果，这些临床 在成年和发育中的大鼠中产生的相关病变。 海马子区CA 3或“末端叶片”的病变将在 由脑室内的红藻氨酸产生 海马病变 子场CA 1，或“索默扇区”，将由瞬态产生 前脑缺血 癫痫发生的研究进展 剩余的神经元将通过体内皮层下 海马切片中的记录或体外记录 准备. 将进一步分析每种治疗， 确定神经可塑性重排在 海马体可能促进或预防癫痫发生。 海马抑制性神经元和受体的完整性 GABA将通过GAD免疫细胞化学测定， 定量体外放射自显影。 海马改变 兴奋功能将由类似的 免疫细胞化学和放射自显影法 谷氨酸及其几种突触后受体亚型。 具体的假设包括：1）CA 3病变会产生 成人癫痫发生，正如已经证明的那样;他们 在新生儿中产生时不会引起癫痫， 因为不同的反应性发芽模式， 海马; 2）CA 1的损失将是癫痫时产生的 在年轻和成年动物中;年轻动物可能更多 严重影响，主要是由于广泛的复发性兴奋性 CA 3区神经元侧支出芽; 3）致癫痫 治疗将伴随着异常的形态学和 抑制性和兴奋性神经元之间的功能相互作用 海马体中的神经递质 免疫反应性和受体。 拟议的工作将提供一个必要的数据体， 在人类中经常观察到的病变的后果 海马体。 它将进一步确定年龄的依赖性， 病变后遗症。 这些信息可以为以下方面提供基础： 评估干预治疗的需要，并设计干预治疗， 遭受损伤产生的创伤的临床人群 和/或癫痫发作。

Several patterns of hippocampal cell loss are observed in the clinical population with focal epilepsy of temporal lobe origin. It is generally agreed that seizures, with associated ischemic/hypoxic distress, predate this hippocampal damage. Once produced, however, there has been little work to determine if this cell damage contributes to the progression of epilepsy. The present proposal examines the acute and chronic physiologic, morphologic and neurochemical consequences of these clinically relevant lesions produced in both adult and developing rats. Lesions of hippocampal subfield CA3, or the "end blade", will be produced by intraventricular kainic acid. Lesions of hippocampal subfield CA1, or "Sommer's sector", will be produced by transient forebrain ischemia. The development of epileptogenesis in remaining neurons will be determined by in vivo subcortical recording or in vitro recording in the hippocampal slice preparation. Each treatment will be analyzed further to determine contributing neuroplastic rearrangements in hippocampus which may promote, or prevent, epileptogenesis. The integrity of hippocampal inhibitory neurons and receptors for GABA, will be determined by GAD immunocytochemistry and quantitative in vitro autoradiography. Alterations in hippocampal excitatory function will be determined by similar immunocytochemical and autoradiographic methods examining glutamate and its several post-synaptic receptor subtypes. Specific hypotheses include: 1) lesions of CA3 will produce epileptogenesis in adults, as has already been demonstrated; they will not be epiletogenic when produced in neonates, primarily because of a different pattern of reactive sprouting in hippocampus; 2) loss of CA1 will be epileptogenic when produced in both young and adult animals; young animals may be more severely affected primarily due to extensive recurrent excitatory collateral sprouting in remaining CA3 neurons; 3) epileptogenic treatments will be accompanied by abnormal morphologic and functional interactions between inhibitory and excitatory neurons in the hippocampus and by specific changes in transmitter immunoreactivity and receptors. The work proposed will provide a needed body of data on the consequences of lesions frequently observed in human hippocampus. It will further identify the age dependence of the lesions sequelae. Such information could provide a foundation for assessing the need for, and designing, interventive treatments in the clinical population suffering from lesion producing trauma and/or seizures.