Experimental mouse model of NMOSD produced by facilitated brain delivery of NMO-IgG by microbubble-enhanced low-frequency ultrasound in experimental allergic encephalomyelitis mice
Experimental mouse model of NMOSD produced by facilitated brain delivery of NMO-IgG by microbubble-enhanced low-frequency ultrasound in experimental allergic encephalomyelitis mice
复制标题
通过微泡增强低频超声促进实验性过敏性脑脊髓炎小鼠脑部递送 NMO-IgG 产生 NMOSD 实验性小鼠模型
DOI：
10.1016/j.msard.2020.102473
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发表时间：
2020-11-01
影响因子：
4
通讯作者：
Guan, Yangtai
中科院分区：
文献类型：
--
作者：
Luo, Jiaying;Xie, Chong;Guan, Yangtai
尽管视神经炎和脊髓炎是视神经脊髓炎谱系疾病（NMOSD）的核心临床特征，但缺乏合适的伴有脊髓炎和视神经炎的 NMOSD 动物模型。我们通过微泡增强低频超声（MELFUS）可逆性血脑屏障（BBB）开放后，向实验性过敏性脑脊髓炎（EAE）小鼠静脉注射100μg视神经脊髓炎免疫球蛋白G抗体（NMO-IgG）和补体，建立了NMOSD小鼠模型。通过组织病理学评估动物。我们发现，脊髓、大脑和视神经中水通道蛋白 4 (AQP4) 和神经胶质原纤维酸性蛋白 (GFAP) 表达缺失，同时出现明显的炎症和脱髓鞘现象，以及人 IgG 和 C9neo 沉积。因此，在MELFUS的帮助下，我们通过应用相当低剂量的人NMOIgG建立了以NMOSD为核心病变的NMOSD小鼠模型，这可能有助于确定发病机制并促进未来其他神经免疫疾病模型的开发。
Although optic neuritis and myelitis are the core clinical characteristics of neuromyelitis optica spectrum disorders (NMOSD), appropriate animal models of NMOSD with myelitis and optic neuritis are lacking. we developed a mouse model of NMOSD by intravenously injecting 100 mu g neuromyelitis optica immunoglobulin G antibody (NMO-IgG) and complement into experimental allergic encephalomyelitis (EAE) mice after reversible blood-brain barrier (BBB) opening by microbubble-enhanced low-frequency ultrasound (MELFUS). Animals were assessed by histopathology. We found noticeable inflammation and demyelination concomitant with the loss of aquaporin-4 (AQP4) and glial fibrillary acidic protein (GFAP) expression in the spinal cord, brain and optic nerve, as well as human IgG and C9neo deposition. Thus, with the help of MELFUS, we established an NMOSD mouse model with the core lesions of NMOSD by applying a considerably lower dose of human NMOIgG, which may help identify the pathogenesis and facilitate the development of other neuroimmune disease models in the future.