title: Characterization of brain inflammation during primary amoebic meningoencephalitis.
abstract: Naegleria fowleri is a free-living amoeba and the etiologic agent of primary amoebic meningoencephalitis (PAM). Trophozoites reach the brain by penetrating the olfactory epithelium, and invasion of the olfactory bulbs results in an intense inflammatory reaction. The contribution of the inflammatory response to brain damage in experimental PAM has not been delineated. Using both optical and electron microscopy, we analyzed the morphologic changes in the brain parenchyma due to inflammation during experimental PAM. Several N. fowleri trophozoites were observed in the olfactory bulbs 72 h post-inoculation, and the number of amoebae increased rapidly over the next 24 h. Eosinophils and neutrophils surrounding the amoebae were then noted at later times during infection. Electron microscopic examination of the increased numbers of neutrophils and the interactions with trophozoites indicated an active attempt to eliminate the amoebae. The extent of inflammation increased over time, with a predominant neutrophil response indicating important signs of damage and necrosis of the parenchyma. These data suggest a probable role of inflammation in tissue damage. To test the former hypothesis, we used CD38-/- knockout mice with deficiencies in chemotaxis to compare the rate of mortality with the parental strain, C57BL/6J. The results showed that inflammation and mortality were delayed in the knockout mice. Based on these results, we suggest that the host inflammatory response and polymorphonuclear cell lysis contribute to a great extent to the central nervous system tissue damage.
authors: Department of Experimental Pathology, Center for Research and Advanced Studies, National Polytechnic Institute, Mexico City, Mexico.
authors: Isaac
authors: I
authors: Cervantes-Sandoval
authors: José de Jesús
authors: Jde J
authors: Serrano-Luna
authors: Ethel
authors: E
authors: García-Latorre
authors: Víctor
authors: V
authors: Tsutsumi
authors: Mineko
authors: M
authors: Shibayama
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000235:genetics; D000562:Amebiasis / Q000276:immunology / Q000401:mortality / Q000469:parasitology / Q000503:physiopathology; D000818:Animals; D001921:Brain / Q000276:immunology / Q000503:physiopathology / Q000648:ultrastructure; D020808:Central Nervous System Protozoal Infections / Q000276:immunology / Q000401:mortality / Q000469:parasitology / Q000503:physiopathology; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000401:mortality / Q000469:parasitology / Q000503:physiopathology; D008297:Male; D008590:Meningoencephalitis / Q000276:immunology / Q000401:mortality / Q000469:parasitology / Q000503:physiopathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D016848:Naegleria fowleri / Q000472:pathogenicity*
chemical_list: D051997:ADP-ribosyl Cyclase 1