A preliminary neuropathological study of Japanese encephalitis in humans and a mouse model

A preliminary neuropathological study of Japanese encephalitis in humans and a mouse model
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DOI:
10.1016/j.trstmh.2006.02.008
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发表时间:
2006-12-01
影响因子:
2.2
通讯作者:
Solomon, Tom
Solomon, Tom
中科院分区:
医学4区
文献类型:
--
作者:
German, Allison C.;Myint, Khin Saw Aye;Solomon, Tom

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日本脑炎病毒是一种由蚊子传播的黄病毒,每年在亚洲造成约10000人死亡。短暂的病毒血症后,病毒进入中枢神经系统,但穿越血脑屏障的途径尚不确定。我们使用常规组织学染色、免疫组织学和电子显微镜检查了四个致命的人类病例的脑组织材料,并与来自小鼠模型的材料进行了比较。如前所述,人体材料中有水肿、血管周围炎症、出血、小胶质细胞结节和无细胞坏死灶。此外,有新的证据表明病毒在血管内皮细胞中复制,内皮细胞受损;这包括偶尔的病毒抗原染色,血管内皮细胞与Ulex uropaeus凝集素I的结合不均匀,以及超微结构的变化。在神经元中也发现了病毒抗原。胶质纤维酸性蛋白染色显示有活跃的星形胶质细胞反应,主要组织相容性复合体II类表达增加表明小胶质细胞激活。在小鼠脑组织中也观察到类似的炎性渗透和小胶质细胞反应。此外,β-淀粉样前体蛋白染色显示轴突运输受损。这些发现是否由血管内皮细胞中的病毒复制或免疫反应引起,值得进一步研究。(C)2006年皇家热带医学和卫生学会。爱思唯尔有限公司出版。保留所有权利。
Japanese encephalitis virus is a mosquito-borne flavivirus that causes approximately 10000 deaths annually in Asia. After a brief viraemia, the virus enters the central nervous system, but the means of crossing the blood-brain barrier is uncertain. We used routine histological staining, immunohistology and electron microscopy to examine brain material from four fatal human cases, and made comparisons with material from a mouse model. In human material there was oedema, perivascular inflammation, haemorrhage, microglial nodules and acellular necrotic foci, as has been described previously. In addition, there was new evidence suggestive of viral replication in the vascular endothelium, with endothelial cell damage; this included occasional viral antigen staining, uneven binding of the vascular endothelial cells to Ulex europaeus agglutinin I and ultrastructural changes. Viral antigen was also found in neurons. There was an active astrocytic response, as shown by glial fibrillary acidic protein staining, and activation of microglial cells was demonstrated by an increase in major histocompatibility complex class II expression. Similar inflammatory infiltrates and a microglial reaction were observed in mouse brain tissue. In addition, beta-amyloid precursor protein staining indicated impaired axonal transport. Whether these findings are caused by viral replication in the vascular endothelium or the immune response merits further investigation. (C) 2006 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved.