Tomikawa Emi, Mutsuga Mayu, Hara Kojiro, Kaneko Chihiro, Togashi Yuko, Miyamoto Yohei
1 Pharmaceutical Research Laboratories, Toray Industries, Inc., Kanagawa, Japan.
2 Clinical Research Department, Toray Industries, Inc., Tokyo, Japan.
Toxicol Pathol. 2019 Jun;47(4):542-552. doi: 10.1177/0192623319838993. Epub 2019 Apr 15.
Experimental autoimmune neuritis (EAN) is an animal model for Guillain-Barré syndrome (GBS), which results in neurological symptoms and histopathological changes in peripheral nerves. In this model, the correlation between the progression of the disease and the histopathological changes is not clear. To further examine histopathological changes in peripheral nerves in EAN rats, sciatic nerves were sampled at onset (day 10), peak (day 16), and recovery (days 22 and 25) of neurological symptoms in P2(57-81)-peptide-administered rats. Axon and myelin degeneration was observed by light microscopy at onset, degeneration became severe at peak, and persisted at recovery. Densities of myelinated nerve fibers and myelin areas decreased from day 10 to a minimum on day 22. Slight axon and myelin degeneration, such as accumulation of vesicles in axons and focal myelin splitting and folding, was observed by transmission electron microscopy at onset; severe degeneration, such as axonal loss, myelin ovoid, and demyelination, increased at peak; and regenerative changes, such as remyelination and enlargement of Schwann cell cytoplasm, occurred at recovery. These results suggest that EAN rats have histopathological similarities to some types of GBS patients and that EAN rats are a useful model to understand the pathogenesis of GBS.
实验性自身免疫性神经炎（EAN）是格林-巴利综合征（GBS）的动物模型，可导致周围神经出现神经症状和组织病理学变化。在该模型中，疾病进展与组织病理学变化之间的相关性尚不清楚。为了进一步研究EAN大鼠周围神经的组织病理学变化，在给予P2(57-81)-肽的大鼠出现神经症状的起始阶段（第10天）、高峰期（第16天）和恢复阶段（第22天和第25天）采集坐骨神经样本。起始阶段通过光学显微镜观察到轴突和髓鞘变性，高峰期变性变得严重，并在恢复阶段持续存在。有髓神经纤维密度和髓鞘面积从第10天到第22天降至最低。起始阶段通过透射电子显微镜观察到轻微的轴突和髓鞘变性，如轴突内囊泡积聚以及局灶性髓鞘分裂和折叠；高峰期严重变性增加，如轴突丢失、髓鞘卵圆体和脱髓鞘；恢复阶段出现再生变化，如髓鞘再生和施万细胞胞质增大。这些结果表明，EAN大鼠与某些类型的GBS患者具有组织病理学相似性，且EAN大鼠是理解GBS发病机制的有用模型。
