Preferential brain homing following intranasal administration of Trypanosoma cruzi.
The Chagas' disease parasite Trypanosoma cruzi commonly infects humans through skin abrasions or mucosa from reduviid bug excreta. Yet most studies on animal models start with subcutaneous or intraperitoneal injections, a distant approximation of the skin abrasion route. We show here that atraumatic placement of T. cruzi in the mouse nasal cavity produced low parasitemia, high survival rates, and preferential brain invasion compared to the case with subcutaneously injected parasites. Brain invasion was particularly prominent in the basal ganglia, peaked at a time when parasitemia was no longer detectable, and elicited a relatively large number of inflammatory foci. Yet, based on motor behavioral parameters and staining with Fluoro-Jade C, a dye that specifically recognizes apoptotic and necrotic neurons, brain invasion did not cause neurodegenerative events, in contrast to the neurodegeneration in the enteric nervous system. The results indicate that placement of T. cruzi on the mucosa in the mouse nasal cavity establishes a systemic infection with a robust yet harmless infection of the brain, seemingly analogous to disease progression in humans. The model may facilitate studies designed to understand mechanisms underlying T. cruzi infection of the central nervous system.
Caradonna
Kacey
K
Parasitology Research Center, Department of Pathology, Tufts University School of Medicine, 150 Harrison Avenue, Boston, MA 02111, USA.
Pereiraperrin
Mercio
M
D000281:Administration, Intranasal; D000818:Animals; D001479:Basal Ganglia / Q000469:parasitology; D001921:Brain / Q000469:parasitology*; D014355:Chagas Disease / Q000401:mortality / Q000469:parasitology / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009296:Nasal Cavity / Q000469:parasitology*; D018512:Parasitemia / Q000401:mortality / Q000469:parasitology; D016133:Polymerase Chain Reaction / Q000379:methods; D014349:Trypanosoma cruzi / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity*