Neuropathology in Neonatal Mice After Experimental Coxsackievirus B2 Infection Using a Prototype Strain, Ohio-1
Neuropathology in Neonatal Mice After Experimental Coxsackievirus B2 Infection Using a Prototype Strain, Ohio-1
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使用原型菌株 Ohio-1 实验性感染柯萨奇病毒 B2 后新生小鼠的神经病理学
DOI：
10.1093/jnen/nlz124
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发表时间：
2019
影响因子：
3.2
通讯作者：
Nagata Noriyo
中科院分区：
文献类型：
--
作者：
Ushioda Waka;Kotani Osamu;Kawachi Kengo;Iwata-Yoshikawa Naoko;Suzuki Tadaki;Hasegawa Hideki;Shimizu Hiroyuki;Takahashi Kimimasa;Nagata Noriyo
柯萨奇病毒 B (CVB) 可导致新生儿严重发病和死亡，有时与急性重症病毒性脑脊髓炎引起的严重脑损伤有关。然而，CVB 感染的神经病理学仍不清楚。柯萨奇病毒 B2 (Ohio-1) 的原型株可引起新生小鼠脑损伤，导致圆顶形头部、脑室扩大和大脑皮层丧失。在这里，我们表征了该小鼠模型中的神经胶质病理学。磁共振成像显示接种后两周内大脑皮层缺失。组织病理学表明，病毒复制引发小胶质细胞和星形胶质细胞的激活，并诱导皮质细胞凋亡，出现严重坏死和侧脑室扩张。相比之下，脑干和小脑在形态上保持完整。免疫组织化学显示，皮质、海马、丘脑和中脑的成熟神经元中柯萨奇病毒和腺病毒受体（CVB 的主要受体）高表达，表明这些区域的成熟神经元受到 CVB2 感染。然而，激活的小胶质细胞和星形胶质细胞的细胞凋亡和神经炎症在丘脑和皮质区域有所不同。病毒抗原在恢复期血清转化的动物大脑中保留。该动物模型将有助于更好地了解 CVB 感染的神经病理学。
Coxsackievirus B (CVB) causes severe morbidity and mortality in neonates and is sometimes associated with severe brain damage resulting from acute severe viral encephalomyelitis. However, the neuropathology of CVB infection remains unclear. A prototype strain of coxsackievirus B2 (Ohio-1) induces brain lesions in neonatal mice, resulting in dome-shaped heads, ventriculomegaly, and loss of the cerebral cortex. Here, we characterized the glial pathology in this mouse model. Magnetic resonance imaging revealed an absence of the cerebral cortex within 2 weeks after inoculation. Histopathology showed that virus replication triggered activation of microglia and astrocytes, and induced apoptosis in the cortex, with severe necrosis and lateral ventricular dilation. In contrast, the brainstem and cerebellum remained morphologically intact. Immunohistochemistry revealed high expression of the coxsackievirus and adenovirus receptor (a primary receptor for CVB) in mature neurons of the cortex, hippocampus, thalamus, and midbrain, demonstrating CVB2 infection of mature neurons in these areas. However, apoptosis and neuroinflammation from activated microglia and astrocytes differed in thalamic and cortical areas. Viral antigens were retained in the brains of animals in the convalescence phase with seroconversion. This animal model will contribute to a better understanding of the neuropathology of CVB infection.