Pyka-Fosciak Grazyna, Stasiolek Mariusz, Litwin Jan A
Department of Histology, Jagiellonian University Medical College, Krakow, Poland.
Folia Histochem Cytobiol. 2018;56(3):151-158. doi: 10.5603/FHC.a2018.0018. Epub 2018 Sep 6.
Experimental autoimmune encephalomyelitis (EAE) is a widely used animal model for studying immunopathology of multiple sclerosis (MS) because it repeats the hallmarks of the human disease, such as focal inflammation and demyelination of the central nervous system, subsequently leading to axonal and neuronal loss. The interrelationships, timing and sequence of different pathological processes that lead to histologically observed lesions in SM are still incompletely understood.
EAE was induced in female C57Bl/6 mice by active immunization with MOG35-55 antigen. Development of the neurological symptoms in the animals was monitored and on that basis spinal cords were collected in three successive phases of the disease (onset, peak, chronic). Total leukocytes, T cells, macrophages/microglia, oligodendrocytes, damaged axons and surviving neuronal cell bodies were visualized using appropriate immunohistochemical markers and their density was quantitatively assessed using image analysis software.
The density of all studied cells except neurons was significantly higher in EAE mice than in the control mice. The density of total leukocytes, T cells, and damaged axons increased from the onset to the peak phase and decreased in the chronic phase to reach values lower than those in the peak phase. The density of macrophages/microglia increased in the peak phase and remained at the elevated level in the chronic phase. Oligodendrocytes showed the highest density in the onset phase and gradually decreased afterwards. The density of neuronal cell bodies decreased only in the chronic phase of the disease.
In mouse model of EAE, inflammatory cells predominate in the early phases of the disease. This study shows for the first time that inflammation precedes oligodendrocyte death and neuronal loss and that macrophages/ microglia are the only cells persisting in large numbers in the chronic phase of the disease, probably because of the switch from proinflammatory to anti-inflammatory phenotype.
实验性自身免疫性脑脊髓炎（EAE）是一种广泛用于研究多发性硬化症（MS）免疫病理学的动物模型，因为它重现了人类疾病的特征，如中枢神经系统的局灶性炎症和脱髓鞘，随后导致轴突和神经元丢失。导致SM组织学观察到病变的不同病理过程之间的相互关系、时间和顺序仍未完全了解。
通过用MOG35-55抗原主动免疫雌性C57Bl/6小鼠诱导EAE。监测动物神经症状的发展，并在此基础上在疾病的三个连续阶段（发病、高峰期、慢性期）收集脊髓。使用适当的免疫组织化学标记物对总白细胞、T细胞、巨噬细胞/小胶质细胞、少突胶质细胞、受损轴突和存活的神经元细胞体进行可视化，并使用图像分析软件对其密度进行定量评估。
除神经元外，所有研究细胞的密度在EAE小鼠中均显著高于对照小鼠。总白细胞、T细胞和受损轴突的密度从发病期到高峰期增加，在慢性期降低至低于高峰期的值。巨噬细胞/小胶质细胞的密度在高峰期增加，并在慢性期保持在升高水平。少突胶质细胞在发病期显示出最高密度，随后逐渐降低。神经元细胞体的密度仅在疾病的慢性期降低。
在EAE小鼠模型中，炎症细胞在疾病早期占主导地位。本研究首次表明炎症先于少突胶质细胞死亡和神经元丢失，并且巨噬细胞/小胶质细胞是疾病慢性期唯一大量持续存在的细胞，可能是因为从促炎表型转变为抗炎表型。
