Institute for Parasitology, Centre for Infection Medicine, University of Veterinary Medicine Hannover, Buenteweg 17, 30559, Hanover, Germany.
Bayer Animal Health, Alfred-Nobel-Str. 50, 40789, Monheim am Rhein, Germany.
Parasitol Res. 2019 Sep;118(9):2591-2600. doi: 10.1007/s00436-019-06395-7. Epub 2019 Jul 27.
Infective larvae of Toxocara canis and T. cati, the common roundworms of dogs and cats, may invade the central nervous system of paratenic hosts, including humans, causing neurotoxocarosis (NT). Previous studies on NT in the model organism "mouse" have indicated distinct differences between T. canis and T. cati regarding larval migration patterns as well as the severity of clinical symptoms and behavioural alterations. The objective of the present study was to provide an extensive characterization of the underlying histopathological alterations, comparing T. canis- and T. cati-induced changes in different brain areas over the course of murine infection. Four histological sections of five brains each of T. canis- and T. cati-infected as well as uninfected C57Bl/6 mice were investigated 7, 14, 28, 42, 70 and 98 days post infection (dpi), while brains of T. cati-infected and control mice were also available 120 and 150 dpi. In addition to haematoxylin-eosin and luxol fast blue-cresyl violet staining, immunohistochemistry was employed to study microglia/macrophage cell morphology and to detect accumulation of β-amyloid precursor protein (β-APP) as an indicator of axonal damage. Haemorrhages, eosinophilic vasculitis and activated microglia/macrophages were detected in both infection groups starting 7 dpi, followed by eosinophilic meningitis in cerebra as from 14 dpi. Overall, little differences in the proportion of animals affected by these alterations were found between the two infection groups. In contrast, the proportion of animals displaying β-APP accumulation was significantly higher in the T. canis than T. cati group as from 28 dpi regarding the cerebrum as well as at 98 dpi regarding the cerebellum. In T. canis-infected mice, myelinophagic microglia/macrophages ("gitter cells") appeared as from 14 dpi, whereas these were first observed at 70 dpi in T. cati-infected animals. The proportion of animals displaying demyelination and/or gitter cells in the cerebrum was significantly higher in the T. canis than T. cati group as from 28 dpi, and at 28 and 42 dpi regarding the cerebellum. Earlier and more severe neurodegeneration during T. canis- than T. cati-induced NT, especially in the cerebrum, may explain the differences in behavioural alterations observed in previous studies. In addition to differences in larval migration preferences, immunological processes may contribute to these patterns, which warrant further investigation.
犬弓首蛔虫和猫弓首蛔虫的感染性幼虫可能会侵入包括人类在内的中间宿主的中枢神经系统，引起神经蚴虫病（NT）。先前在“小鼠”这一模式生物上对 NT 的研究表明，犬弓首蛔虫和猫弓首蛔虫在幼虫迁移模式以及临床症状和行为改变的严重程度方面存在明显差异。本研究的目的是提供对潜在组织病理学改变的广泛描述，比较在感染过程中不同脑区中由犬弓首蛔虫和猫弓首蛔虫引起的变化。用感染和未感染 C57Bl/6 小鼠的每组 5 只脑的 4 个组织切片，在感染后 7、14、28、42、70 和 98 天（dpi）进行研究，而猫弓首蛔虫感染和对照组的小鼠的脑也在 120 和 150 dpi 时进行研究。除了苏木精-伊红和卢索快速蓝-甲苯胺蓝染色外，还进行了免疫组织化学染色以研究小胶质细胞/巨噬细胞形态，并检测 β-淀粉样前体蛋白（β-APP）的积累，作为轴突损伤的指标。在感染后 7 天，两组感染均出现了出血、嗜酸性血管炎和活化的小胶质细胞/巨噬细胞，随后在 14 天出现了脑的嗜酸性脑膜炎。总的来说，两组感染动物受这些改变影响的比例差异不大。相反，在感染后 28 天的大脑和 98 天的小脑，与猫弓首蛔虫感染相比，犬弓首蛔虫感染动物的 β-APP 积累比例显著更高。在感染后 14 天，犬弓首蛔虫感染的小鼠出现了吞噬髓磷脂的小胶质细胞/巨噬细胞（“网格细胞”），而猫弓首蛔虫感染的动物则在 70 天观察到这些细胞。在感染后 28 天的大脑和 28 天和 42 天的小脑，与猫弓首蛔虫感染相比，犬弓首蛔虫感染的动物出现脱髓鞘和/或网格细胞的比例显著更高。与猫弓首蛔虫感染相比，犬弓首蛔虫感染引起的 NT 早期和更严重的神经退行性变，尤其是在大脑中，可能解释了先前研究中观察到的行为改变差异。除了幼虫迁移偏好的差异外，免疫过程也可能导致这些模式，这值得进一步研究。
