Xiong Huihui, Zhou Zongpu, Wu Zhongdao, Feng Ying, Xie Fukang
Histology and Embryology Department of Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
School of Medicine, South China University of Technology, Guangzhou, China.
Anat Rec (Hoboken). 2021 May;304(5):1084-1093. doi: 10.1002/ar.24538. Epub 2020 Oct 23.
In this study, we present a new model for demyelination of the central nervous system (CNS). BALB/c mice were infected with Angiostrongylus cantonensis and analyzed 7, 14, and 21 days postinfection. Neurological scale evaluation, magnetic resonance imaging (MRI), histology, real-time quantitative polymerase chain reaction, and western blotting were all performed on days 7, 14, and 21. The results showed that the neurological functions and weight of A. cantonensis-infected mice decreased markedly after 21 days of infection. MRI showed subdural effusion and white high signals in the corpus callosum in both T1WI and T2WI, while hematoxylin and eosin and luxol fast blue staining showed hemorrhage and demyelination in the corpus callosum. Transmission electron microscopy revealed that the ultrastructure of the myelin sheath in the corpus callosum was dispersed or disintegrated. The percentage of myelinated axons was significantly decreased, and the g-ratio was lower than that in the normal group. Both protein and mRNA levels of myelin basic protein decreased markedly at 21 days postinfection. Immunofluorescence revealed that the number of CC1 positive cells in the corpus callosum also decreased, which confirmed the damage of A. cantonensis to oligodendrocytes. Our experiments confirmed that A. cantonensis infection caused demyelination in the CNS of BALB/c mice after 21 days, and its clinical manifestations and pathological changes were similar to those of multiple sclerosis and other CNS demyelination models. Thus, mice infected with A. cantonensis could be used as a new model to study acute demyelination of the CNS.
在本研究中，我们提出了一种新的中枢神经系统（CNS）脱髓鞘模型。将BALB/c小鼠感染广州管圆线虫，并在感染后7天、14天和21天进行分析。在第7天、14天和21天均进行了神经功能评分评估、磁共振成像（MRI）、组织学、实时定量聚合酶链反应和蛋白质印迹分析。结果显示，感染广州管圆线虫的小鼠在感染21天后神经功能和体重显著下降。MRI显示在T1WI和T2WI序列中，硬膜下积液以及胼胝体出现白色高信号，而苏木精-伊红染色和Luxol固蓝染色显示胼胝体有出血和脱髓鞘。透射电子显微镜显示胼胝体髓鞘的超微结构分散或解体。有髓轴突的百分比显著降低，g比值低于正常组。感染后21天，髓鞘碱性蛋白的蛋白质和mRNA水平均显著下降。免疫荧光显示胼胝体中CC1阳性细胞数量也减少，这证实了广州管圆线虫对少突胶质细胞的损伤。我们的实验证实，广州管圆线虫感染在21天后导致BALB/c小鼠中枢神经系统脱髓鞘，其临床表现和病理变化与多发性硬化症和其他中枢神经系统脱髓鞘模型相似。因此，感染广州管圆线虫的小鼠可作为研究中枢神经系统急性脱髓鞘的新模型。
