title: Late stage infection in sleeping sickness.
abstract: 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.
authors.affiliation: Institute of Pathology and Neuropathology, University of Tübingen, Tübingen, Germany.
authors.forename: Hartwig
authors.initials: H
authors.lastname: Wolburg
authors.forename: Stefan
authors.initials: S
authors.lastname: Mogk
authors.forename: Sven
authors.initials: S
authors.lastname: Acker
authors.forename: Claudia
authors.initials: C
authors.lastname: Frey
authors.forename: Monika
authors.initials: M
authors.lastname: Meinert
authors.forename: Caroline
authors.initials: C
authors.lastname: Schönfeld
authors.forename: Michael
authors.initials: M
authors.lastname: Lazarus
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Urade
authors.forename: Bruno Kilunga
authors.initials: BK
authors.lastname: Kubata
authors.forename: Michael
authors.initials: M
authors.lastname: Duszenko
mesh_terms: D000818:Animals; D001921:Brain / Q000469:parasitology; D003470:Culture Media; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D051381:Rats; D017208:Rats, Wistar; D014346:Trypanosoma brucei brucei / Q000302:isolation & purification; D014353:Trypanosomiasis, African / Q000097:blood / Q000473:pathology*
chemical_list: D003470:Culture Media