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Abstract：
It is textbook knowledge that human infective forms of Trypanosoma brucei, the causative agent of sleeping sickness, enter the brain across the blood-brain barrier after an initial phase of weeks (rhodesiense) or months (gambiense) in blood. Based on our results using an animal model, both statements seem questionable. As we and others have shown, the first infection relevant crossing of the blood brain border occurs via the choroid plexus, i.e. via the blood-CSF barrier. In addition, counting trypanosomes in blood-free CSF obtained by an atlanto-occipital access revealed a cyclical infection in CSF that was directly correlated to the trypanosome density in blood infection. We also obtained conclusive evidence of organ infiltration, since parasites were detected in tissues outside the blood vessels in heart, spleen, liver, eye, testis, epididymis, and especially between the cell layers of the pia mater including the Virchow-Robin space. Interestingly, in all organs except pia mater, heart and testis, trypanosomes showed either a more or less degraded appearance of cell integrity by loss of the surface coat (VSG), loss of the microtubular cytoskeleton and loss of the intracellular content, or where taken up by phagocytes and degraded intracellularly within lysosomes. This is also true for trypanosomes placed intrathecally into the brain parenchyma using a stereotactic device. We propose a different model of brain infection that is in accordance with our observations and with well-established facts about the development of sleeping sickness.
摘要：
这是教科书上的知识，人类感染形式的锥虫，昏睡病的病原体，在血液中的初始阶段（罗得西亚）或几个月（冈比亚）后，通过血脑屏障进入大脑。根据我们使用动物模型的结果，这两种说法似乎都值得怀疑。正如我们和其他人所表明的，第一次感染相关的血脑边界通过脉络丛发生，即通过血液-CSF屏障。此外,对通过寰枕骨通路获得的无血CSF中的锥虫进行计数显示，CSF中存在周期性感染，这与血液感染中的锥虫密度直接相关。我们还获得了器官浸润的确凿证据，因为在心脏血管外的组织中检测到寄生虫，脾,脾肝脏,眼睛,睾丸,附睾,尤其是在软脑膜的细胞层之间，包括Virchow-Robin空间。有趣的是,除了软脑膜以外的所有器官,心脏和睾丸,锥虫通过表面涂层（VSG）的损失显示出或多或少降解的细胞完整性外观，微管细胞骨架的丧失和细胞内内容物的丧失，或被吞噬细胞吸收并在溶酶体内胞内降解的地方。对于使用立体定向装置鞘内置于脑实质中的锥虫也是如此。我们提出了一种不同的大脑感染模型，该模型与我们的观察结果以及有关昏睡病发展的公认事实相一致。
