急性全身性癫痫发作海马神经元丢失特征(实验研究)

G. Demyashkin, Migran S. Grigoryan, Ivan V. Vetrov, Fedor V. Vetrov, V.P. Rauzheva, I. Zorin, E. Shapovalova
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摘要

背景:今天,癫痫是最常见的神经系统疾病之一。尽管几个多世纪以来对癫痫发生的研究和治疗方案的发展,这种疾病的神经生物学基础仍然知之甚少。目前已知的可靠证据是,癫痫患者海马神经元数量减少,神经胶质瘤:内侧颞叶硬化(海马硬化),但与癫痫发作的因果关系尚未确定。在急性癫痫发作的背景下评估海马神经元的存活是特别有趣的,这将允许确定神经组织退行性变化的机制。目的:本研究的目的是免疫组织化学方法评估急性癫痫发作时海马中NeuN和caspase-8的水平。材料与方法:以CBA种群雄性小鼠为模型。随机分为两组:第一组(28只)腹腔注射戊四唑模拟急性癫痫发作,第二组(20只)对照组。对海马碎片、CA1、CA3和齿状回进行组织学和免疫组化研究。结果:ⅰ组大鼠均出现全发性癫痫发作。注射戊四唑24 h后,海马锥体神经元在CA3区出现最弱的NeuN(轻核)标记。与caspase-8反应时,在CA3区观察到相同的免疫表型模式,表明注射戊四唑24小时后,免疫阳性的海马锥体神经元数量增加。结论:以45 g/kg剂量单次注射戊四唑后,免疫组化评价海马NeuN-和caspase-8阳性锥体神经元分布显示:癫痫发作后1天NeuN-阳性神经元减少,caspase-8阳性神经元增加,随后第5天所研究标记物恢复。
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The features of neuronal loss in the hippocampus during acute generalized seizure (experimental study)
BACKGROUND: Today, epilepsy is one of the most frequently diagnosed neurological diseases. Despite more than several centuries of research on epileptogenesis and the development of treatment protocols, the neurobiological basis of the disease remains poorly understood. It is reliably known that patients with epilepsy are found to have a reduced number of hippocampal neurons and gliosis: mesial temporal sclerosis (hippocampal sclerosis), but the causal relationship with seizures has not yet been established. It is of particular interest to evaluate the survival of hippocampal neurons against the background of acute epileptic seizures, which will allow to determine the mechanisms of degenerative changes in nervous tissue. AIM: The aim of the study was to immunohistochemically assess the levels of NeuN and caspase-8 in the hippocampus during acute epileptic seizures. MATERIALS AND METHODS: Male mice of the CBA population were used as models. The animals were divided into groups: 1st (n = 28) simulated acute epileptic seizure by intraperitoneal injection of pentyltetrazole, 2nd (n = 20) control. Histological and immunohistochemical studies were performed on hippocampal fragments, regions: CA1, CA3 and dentate gyrus. RESULTS: Generalized epileptic seizures were noted in all animals of Group I. The weakest labeling of hippocampal pyramidal neurons with NeuN (light nuclei) was observed in CA3 region, which was observed 24 hours after pentyltetrazole injection. The same immunophenotypic pattern was observed in the CA3 region during reaction with caspase-8, which demonstrated an increase in the number of immunopositive hippocampal pyramidal neurons 24 hours after pentyltetrazole injection. CONCLUSIONS: After a single injection of pentyltetrazole at a dose of 45 g/kg, immunohistochemical evaluation of the distribution of NeuN- and caspase-8-positive pyramidal neurons of the hippocampus revealed: a decrease in the NeuN-positive neurons and an increase in caspase-8-positive neurons one day after the seizure with subsequent recovery of the studied markers by day 5.
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