Institute of Pathology and Neuropathology, University of Tübingen, Tübingen, Germany.
PLoS One. 2012;7(3):e34304. doi: 10.1371/journal.pone.0034304. Epub 2012 Mar 27.
At the turn of the 19(th) century, trypanosomes were identified as the causative agent of sleeping sickness and their presence within the cerebrospinal fluid of late stage sleeping sickness patients was described. However, no definitive proof of how the parasites reach the brain has been presented so far. Analyzing electron micrographs prepared from rodent brains more than 20 days after infection, we present here conclusive evidence that the parasites first enter the brain via the choroid plexus from where they penetrate the epithelial cell layer to reach the ventricular system. Adversely, no trypanosomes were observed within the parenchyma outside blood vessels. We also show that brain infection depends on the formation of long slender trypanosomes and that the cerebrospinal fluid as well as the stroma of the choroid plexus is a hostile environment for the survival of trypanosomes, which enter the pial space including the Virchow-Robin space via the subarachnoid space to escape degradation. Our data suggest that trypanosomes do not intend to colonize the brain but reside near or within the glia limitans, from where they can re-populate blood vessels and disrupt the sleep wake cycles.
在 19 世纪之交，人们发现锥虫是昏睡病的病原体，并描述了晚期昏睡病患者脑脊液中存在锥虫。然而，迄今为止，还没有提供寄生虫如何到达大脑的确切证据。通过分析感染后 20 多天的啮齿动物大脑的电子显微镜照片，我们在这里提供了确凿的证据，证明寄生虫首先通过脉络丛进入大脑，然后穿透上皮细胞层到达脑室系统。相反，在血管外的实质组织中没有观察到锥虫。我们还表明，大脑感染取决于长而细的锥虫的形成，并且脑脊液以及脉络丛的基质是不利于锥虫生存的环境，锥虫通过蛛网膜下腔进入软脑膜空间，包括血管周围间隙，以逃避降解。我们的数据表明，锥虫并不打算在大脑中定植，而是位于胶质界膜附近或内部，从那里它们可以重新进入血管并扰乱睡眠-觉醒周期。
