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匹罗卡品诱导癫痫持续状态后小鼠海马区神经元变性和神经胶质增生的时程变化。

Neuronal degeneration and gliosis time-course in the mouse hippocampal formation after pilocarpine-induced status epilepticus.

机构信息

Department of Cell Biology, Biological Sciences Institute, University of Brasília-UnB, Brasília, DF, Brazil.

出版信息

Brain Res. 2012 Aug 27;1470:98-110. doi: 10.1016/j.brainres.2012.06.008. Epub 2012 Jul 8.

Abstract

Temporal lobe epilepsy (TLE) is the most common type of human epilepsy and has been related with extensive loss of hippocampal pyramidal and dentate hilar neurons and gliosis. Many characteristics of TLE are reproduced in the pilocarpine model of epilepsy in mice. This study analyzed the neuronal damage, assessed with Fluoro-Jade (FJB) and cresyl violet, and gliosis, investigated with glial fibrilary acidic protein (GFAP) immunohistochemistry, occurring in the hippocampal formation of mice at 3, 6, 12 and 24h, 1 and 3 weeks after the pilocarpine-induced status-epilepticus (SE) onset. The maximum neuronal damage score and the FJB-positive neurons peak were found in the hilus of dentate gyrus 3 and 12 h after SE onset (P<0.05), respectively. At 1 week after SE onset, the greatest neuronal damage score was detected in the CA1 pyramidal cell layer and the greatest numbers of FJB-positive neurons were found both in the CA1 and CA3 pyramidal cell layers (P<0.05). The molecular, CA3 and CA1 pyramidal cell layers expressed highest presence of GFAP immunoreaction at 1 and 3 weeks after SE onset (P<0.05). Our findings show that, depending on the affected area, neuronal death and gliosis can occur within few hours or weeks after SE onset. Our results corroborate previous studies and characterize short time points of temporal evolution of neuropathological changes after the onset of pilocarpine-induced SE in mice and evidences that additional studies of this temporal evolution may be useful to the comprehension of the cellular mechanisms underlying epileptogenesis.

摘要

颞叶癫痫(TLE)是最常见的人类癫痫类型,与海马锥体和齿状回神经细胞广泛丢失以及神经胶质增生有关。在匹罗卡品诱导的小鼠癫痫模型中重现了许多 TLE 的特征。本研究分析了在匹罗卡品诱导的癫痫持续状态(SE)发作后 3、6、12 和 24 小时、1 和 3 周时,用氟-金胺(FJB)和甲苯胺蓝评估的神经元损伤和用胶质纤维酸性蛋白(GFAP)免疫组化评估的神经胶质增生,在海马结构中发生的情况。在 SE 发作后 3 和 12 小时,齿状回门区的最大神经元损伤评分和 FJB 阳性神经元峰值最高(P<0.05)。在 SE 发作后 1 周,CA1 锥体细胞层的神经元损伤评分最大,CA1 和 CA3 锥体细胞层的 FJB 阳性神经元数量最多(P<0.05)。在 SE 发作后 1 和 3 周,分子层、CA3 和 CA1 锥体细胞层的 GFAP 免疫反应表达最高(P<0.05)。我们的发现表明,根据受影响的区域,神经元死亡和神经胶质增生可能在 SE 发作后数小时或数周内发生。我们的结果与之前的研究一致,并描述了匹罗卡品诱导的 SE 发作后神经病理学变化的短时间点的时间演变,并证明对这种时间演变的进一步研究可能有助于理解癫痫发生的细胞机制。

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