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一组患有拉斯穆森脑炎患者的海马增殖性活动:神经元、胶质细胞和脑源性神经营养因子的组织表达相关性。

Proliferative hippocampal activity in a group of patients with Rasmussen's encephalitis: Neuronal, glial, and BDNF tissue expression correlations.

作者信息

Magno Elane N

机构信息

Laboratory of Experimental Neurology, Federal University of São Paulo, Brazil; Laboratory of Histology, Federal University of Maranhão, Brazil.

出版信息

Epilepsy Behav. 2018 May;82:29-37. doi: 10.1016/j.yebeh.2018.02.022. Epub 2018 Mar 23.

DOI:10.1016/j.yebeh.2018.02.022
PMID:29579552
Abstract

Rasmussen's encephalitis (RE) is a rare and devastating unilateral inflammatory brain disease that causes severe and intractable partial epilepsy. It has been shown that epilepsy and subsequent inflammation have deleterious influence on hippocampal cell survival and neurogenesis, but this still has not been systematically explored in human tissue. In this study, we investigated the correlation between inflammation and epilepsy as well as the rates of hippocampal gliogenesis and neurogenesis in a pediatric group of six patients with RE and six control cases. The dentate gyrus (DG) samples were obtained from patients who underwent surgery for intractable RE. Sections were processed for immunohistochemistry using antibodies against sex determining region Y-box 2 (Sox2), nestin, human protein encoded by MKI67 gen (Ki67), and brain-derived neurotrophic factor (BDNF). There was an increase in the number of Ki67-positive granule cells in the DG of patients with RE in comparison with the autopsy control group, but no statistical difference for Sox2-positive cells was observed between these groups. Nestin immunolabeling was less intense in the RE group while BDNF expression was increased. Neurons that were BDNF-positive were found in DG from patients with RE but not in the control group. In patients with RE, few nestin-positive cells in DG were also positive for BDNF, unlike in controls which showed no colocalization for these two markers. These results suggest a proliferation activity in the DG subfield of patients with RE, and also future studies are necessary to address the role of new cells in the hippocampus of patients with RE.

摘要

拉斯穆森脑炎(RE)是一种罕见且具有破坏性的单侧炎症性脑病,可导致严重且难治的部分性癫痫。研究表明,癫痫及随后的炎症对海马细胞存活和神经发生有有害影响,但在人体组织中尚未对此进行系统研究。在本研究中,我们调查了6例RE患儿和6例对照病例的炎症与癫痫之间的相关性,以及海马神经胶质生成和神经发生的速率。齿状回(DG)样本取自因难治性RE接受手术的患者。使用抗性别决定区Y盒2(Sox2)、巢蛋白、MKI67基因编码的人类蛋白(Ki67)和脑源性神经营养因子(BDNF)的抗体对切片进行免疫组织化学处理。与尸检对照组相比,RE患者DG中Ki67阳性颗粒细胞数量增加,但两组之间Sox2阳性细胞未观察到统计学差异。RE组巢蛋白免疫标记强度较低,而BDNF表达增加。在RE患者的DG中发现了BDNF阳性神经元,而对照组中未发现。在RE患者中,DG中很少有巢蛋白阳性细胞也为BDNF阳性,而对照组中这两种标记物未显示共定位。这些结果表明RE患者DG亚区存在增殖活性,并且未来有必要开展研究以探讨新细胞在RE患者海马中的作用。

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