title: Ependymal damage in a Plasmodium yoelii yoelii lethal murine malaria model.
abstract: Malaria continues to be a major global health problem, and over 40% of the world's population is at risk. Severe or complicated malaria is defined by clinical or laboratory evidence of vital organ dysfunction, including dysfunction of the central nervous system (CNS). The pathogenesis of complicated malaria has not been completely elucidated; however, the development of the multiorgan affection seems to play an important role in the disruption of the blood brain barrier (BBB) that protects the CNS against chemical insults. Historically, the BBB has received more attention in the pathogenesis of malaria than have the cerebrospinal fluid-brain barrier (CSFBB) and ependymal cells. This perspective may be misguided because, in the context of disease or toxicity, the CSFBB is more vulnerable to many foreign invaders than are the capillaries. Given the lack on studies of the damage to the CSFBB and ependymal epithelium in experimental murine malaria, the present study evaluated morphological changes in the ependymal cells of CD-1 male mice infected with lethal Plasmodium yoelii yoelii (Pyy) via histopathology and scanning electron microscopy (SEM). Samples were taken two, four and six days post-infection (PI). No lesions were observed upon the initial infection. By the fourth day PI, fourth ventricle ependymal samples exhibited disruptions and roughened epithelia. More severe injuries were observed at six days PI and included thickened cilia and deep separations between the ependymal intercellular spaces. In some of the analyzed areas, the absence of microvilli and cell layer detachment were observed, and some areas exhibited blebbing surfaces. The ependymal cell lesions observed in the CD1 male mice infected with lethal Pyy seemed to facilitate the paracellular permeability of the CSFBB and consequently promote the access of inflammatory mediators and toxic molecules through the barrier, which resulted in damage to the brain tissue. Understanding the mechanism of ependymal disruption during lethal murine malaria could help to elucidate the local and systemic factors that are involved in the pathogenesis of the disease and may provide essential clues for the prevention and treatment of complicated human malaria.
authors.affiliation: Department of Microbiology and Parasitology, Faculty of Medicine, Autonomous National University of Mexico (UNAM), Mexico City, Mexico. normariv@unam.mx.
authors.forename: Norma
authors.initials: N
authors.lastname: Rivera Fernández
authors.affiliation: Department of Neuroscience, UNAM, Iztacala, Mexico, Mexico.
authors.forename: Laura
authors.initials: L
authors.lastname: Colín Barenque
authors.affiliation: Department of Pathology, Faculty of Veterinary Medicine and Zootechnics, UNAM, México City, Mexico.
authors.forename: Samanta E
authors.initials: SE
authors.lastname: Romero Silva
authors.affiliation: Department of Pathology, Faculty of Veterinary Medicine and Zootechnics, UNAM, México City, Mexico.
authors.forename: Gerardo
authors.initials: G
authors.lastname: Salas Garrido
authors.affiliation: Department of Microbiology and Parasitology, Faculty of Medicine, Autonomous National University of Mexico (UNAM), Mexico City, Mexico.
authors.forename: Samantha G
authors.initials: SG
authors.lastname: Jiménez Rosey
authors.affiliation: Department of Cell Biology, Faculty of Medicine, UNAM, Mexico City, Mexico.
authors.forename: Armando
authors.initials: A
authors.lastname: Zepeda Rodríguez
authors.affiliation: Department of Pathology, Faculty of Veterinary Medicine and Zootechnics, UNAM, México City, Mexico.
authors.forename: Laura P
authors.initials: LP
authors.lastname: Romero Romero
authors.affiliation: Department of Pathology, Faculty of Veterinary Medicine and Zootechnics, UNAM, México City, Mexico.
authors.forename: Ángeles
authors.initials: Á
authors.lastname: Menchaca Gómez
authors.affiliation: Department of Microbiology and Parasitology, Faculty of Medicine, Autonomous National University of Mexico (UNAM), Mexico City, Mexico.
authors.forename: Filiberto
authors.initials: F
authors.lastname: Malagón Gutiérrez
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000469:parasitology / Q000473:pathology; D001921:Brain / Q000469:parasitology / Q000473:pathology; D002452:Cell Count; D002552:Cerebral Ventricles / Q000469:parasitology / Q000473:pathology; D004805:Ependyma / Q000473:pathology*; D008288:Malaria / Q000469:parasitology / Q000473:pathology*; D008297:Male; D008636:Mesencephalon / Q000469:parasitology / Q000473:pathology; D051379:Mice; D010967:Plasmodium yoelii