HIPPOCAMPAL DAMAGE AS A CAUSE OF EPILEPSY

在海马区观察到几种海马细胞丢失的模式 临床人群中起源于颞叶的局灶性癫痫。它 人们普遍认为，癫痫发作与 缺氧性/缺氧性窘迫，先于这种海马区损伤。 然而，一旦生产出来，就几乎没有什么工作要确定了 如果这种细胞损伤导致癫痫的进展。这个 本提案检查急性和慢性生理学， 这些临床表现的形态和神经化学后果 成年大鼠和发育中的大鼠均可产生相应的损伤。 海马区CA3区的损害，或“末端叶片”，将是 由脑室内的红藻氨酸产生。海马区病变 子油田CA1，或“Sommer‘s Sector”将由瞬变油气田生产 前脑缺血。我国癫痫发病机制的研究进展 剩余的神经元将由活体皮质下确定 在海马片上记录或体外记录 准备工作。每种治疗方法都将进一步分析，以 确定在神经可塑性重排中的作用 可能促进或阻止癫痫发生的海马体。 大鼠海马区抑制性神经元和受体的完整性 GABA，将通过GAD免疫细胞化学和 体外定量放射自显影。海马区的改变 兴奋功能将由类似的 免疫细胞化学和放射自显影方法检测 谷氨酸及其几种突触后受体亚型。 具体假设包括：1)CA3的病变会产生 成年人的癫痫发生，正如已经证明的那样；他们 主要是在新生儿身上产生时不会引起癫痫 因为一种不同的反应萌发模式 海马区；2)CA1的缺失在产生时会导致癫痫 在幼年动物和成年动物中；幼年动物可能比 严重影响主要是由于广泛的复发性兴奋性 残存CA3神经元侧枝萌发；3)致痫 治疗会伴随着异常的形态和 抑制性神经元和兴奋性神经元之间的功能相互作用 在海马体中，通过递质的特定变化 免疫反应性和受体。 拟议的工作将提供关于 人类常见病变的后果 海马体。它将进一步确定老年人的年龄依赖性 病变会有后遗症。这些信息可以为 评估干预治疗的需求和设计 创伤性损伤的临床人群 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.