Effects of Acute Chagas'Disease on Mice Central Nervous System

Abstract

This study has been done to evaluate the central nervous system (CNS) of mice infected with Trypanosoma cruzi and its relationships with the irreversible decrease of motor activity of the rear limbs during acute Chagas´disease. The course of the present study shows the in vivo behaviour of three parasites strains which were isolated from different sources and geographical areas, with the purpose of explaining the parasitemia, mortality rate, clinical, pathological and histopathological changes in the CNS of infected mice. The mice were injected intraperitoneally with 5.10 3 bloodstreams of different T. cruzi strains. The mice infected with PR and ASM strains from Venezuela, showed low parasitemia and high mortality, while the Y strain produced higher parasitemia levels. At the 30th day post-infection both left parietal brain cortex (LPC) and spinal cord (SC) were sectioned, stained with hematoxilin and eosin (H-E) and examined by means of confocal ligth microscopy. At this time, the pathology of the CNS exhibited focal infiltrates of monocytes, lymphocytes, plasmocytes, polymorphonuclear cells and loss of neuronas and motoneurons. The sections of LPC of infected mice with ASM strain, showed loss neuronal, parasites and abundant T. cruzi antigen deposits in the proximity of the swollen neurons. The sections of SC stained with Enolase-Avidin-Biotin-Peroxidase showed a reduction in the average number of neurons of the cervical region (CR) of the infected mice with PR, ASM and Y strains. Sections stained with Propidium Ioduro (IP) showed a reduction of the number of motoneurons in all regions of the SC, with a significant difference between groups infected with different T. cruzi strains and control uninfected mice (P < 0.05). This study established a correlation between the parasitism in the proximity to inflammatory cells, together the appearance of T. cruzi antigen and neuronal destruction in the brain. Therefore it can be concluded that the changes in CNS may be attributed to early parasitism in nervous tissue, which occur in a few days, involving clinico-pathological manifestations, which produced alterations of the mobility with paralysis of the rear limbs and death in 100% of mice with acute infection produced by PR and ASM-T. cruzi strains from Venezuela.

Experimental Trypanosoma cruzi Infection Induces Pain in Mice Dependent on Early Spinal Cord Glial Cells and NFκB Activation and Cytokine Production

“…In addition to high serum levels of hyperalgesic cytokines, chronic phase CD patients may present severe neurological manifestations, resulting in elevated morbidity and mortality rates (19). Amastigote forms and T. cruzi granular antigens (this last one restricted to inflamed foci) can be abundantly detected in CNS (cortex and basal nuclei) in the chronic phase of CD in inbred mice, suggesting potential local actions (20,21). There seems to occur an active interaction between T. cruzi and the immune/nervous system because the T. cruzi parasite can be found infecting mouse peripheral glial cells (22)(23)(24); brain astrocytes (25)(26)(27); and spinal cord astrocytes, microglia, and macrophages (24,28) as well as human peripheral glial cells (29), astrocytes (25,30), and neurons (29).…”