Pathology of intracardiac nerves in experimental Chagas disease

Ribeiro, Lidia Cristina Villela; Barbosa, Alynne da Silva; Andrade, Zilton A.

doi:10.1590/s0074-02762002000700016

Cited by 11 publications

(10 citation statements)

References 20 publications

(20 reference statements)

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“…This dysfunction was characterized by a marked reduction in heart rate variability, with reduced variance (time-domain parameter) and the VLF, LF, and HF components (frequency-domain parameters) of heart rate variability, as well as a concurrent reduction in the cardiac vagal effect, without an apparent change in sympathetic effects, as measured by pharmacological blockade in chronic control chagasic animals. Only morphological reports describing the ganglia and nerve lesions in chagasic mice have been published in the literature [36]. This finding follows our previous report of a similar autonomic dysfunction in mice with acute Chagas disease [18].…”

Section: Discussionsupporting

confidence: 88%

Effects of Cholinergic Stimulation with Pyridostigmine Bromide on Chronic Chagasic Cardiomyopathic Mice

Cuba

Machado

Farnesi

et al. 2014

Mediators of Inflammation

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The aim of the present study was to assess the effects of an anticholinesterase agent, pyridostigmine bromide (Pyrido), on experimental chronic Chagas heart disease in mice. To this end, male C57BL/6J mice noninfected (control:Con) or chronically infected (5 months) with Trypanosoma cruzi (chagasic:Chg) were treated or not (NT) with Pyrido for one month. At the end of this period, electrocardiogram (ECG); cardiac autonomic function; heart histopathology; serum cytokines; and the presence of blood and tissue parasites by means of immunohistochemistry and PCR were assessed. In NT-Chg mice, significant changes in the electrocardiographic, autonomic, and cardiac histopathological profiles were observed confirming a chronic inflammatory response. Treatment with Pyrido in Chagasic mice caused a significant reduction of myocardial inflammatory infiltration, fibrosis, and hypertrophy, which was accompanied by a decrease in serum levels of IFNγ with no change in IL-10 levels, suggesting a shift of immune response toward an anti-inflammatory profile. Lower nondifferent numbers of parasite DNA copies were observed in both treated and nontreated chagasic mice. In conclusion, our findings confirm the marked neuroimmunomodulatory role played by the parasympathetic autonomic nervous system in the evolution of the inflammatory-immune response to T. cruzi during experimental chronic Chagas heart disease in mice.

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Section: Discussionsupporting

confidence: 88%

Effects of Cholinergic Stimulation with Pyridostigmine Bromide on Chronic Chagasic Cardiomyopathic Mice

Cuba

Machado

Farnesi

et al. 2014

Mediators of Inflammation

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“…In addition, discontinuous perineurial sheaths have been described for enteric ganglia (Baluk 1995), and these ganglia also develop destructive ganglionitis in chronic Chagas' disease (Köberle 1968;Chapadeiro et al 1991;Maifrino et al 1999). Intracardiac nerves, in contrast, have been found to be surrounded by a GluT-1 + perineurial sheath in the present study and are only mildly affected in experimental Chagas' disease in mice (Ribeiro et al 2002). Incomplete ganglion-tissue barriers may thus contribute to the susceptibility of both enteric and cardiac ganglia to destructive ganglionitis in response to inflammation or infection of the surrounding tissues.…”

Section: Discussionsupporting

confidence: 63%

MHC class II antigen-expressing cells in cardiac ganglia of the rat

Kummer

Stommel

2004

Cell Tissue Res

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Cardiac ganglia develop destructive ganglionitis in chronic Chagas' disease and rheumatic heart disease. This ganglionitis is associated with periganglionic infiltrations and is suspected of developing secondary to epicardial inflammation. If so, it would be expected that cardiac ganglia (1) are equipped with an inventory of immune competent cells allowing the initiation of inflammatory processes, and (2) are not effectively protected from the milieu of the surrounding tissue by metabolically active diffusion barriers. These problems were addressed in specified pathogen-free rats by electron microscopy and immunohistochemistry with markers for dendritic cells, monocytes/macrophages, and perineurial barriers. In contrast to nerve fascicles, cardiac ganglia are only partially enveloped by perineurial cells. Inside the ganglia, ramified cells with major histocompatibility complex class II antigen (reacting with monoclonal antibody OX6) on their surface and exhibiting an ultrastructure typical of dendritic cells are numerous, comprising nearly 5% of all cells within ganglia. The ratio of the number of these cells to that of neurons is 1:2. Cells reacting with monoclonal antibodies ED1 and ED2, markers for monocytes/macrophages, constitute 1.8% and 1.6% of the ganglionic cell population, respectively. Such cells are less frequent in the cervical trunk of the vagus nerve. Thus, the inventory of immune competent cells in rat cardiac ganglia is consistent with the view that the abundance of antigen-presenting cells correlates with the permeability of the barriers providing protection from blood-borne and tissue-borne factors.

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“…In the absence of a neurotoxin or any kind of toxin release by the parasite, the documentation of the lysis of neurons by palisade cytotoxic lymphocytes and target cell depopulations is significant (74,388). This finding suggests that neuronal cell loss correlates with the impairment of neurohormonal circuits (251,298,325,388). Therefore, the neurogenic theory suggests that autoimmune-dependent abnormalities in the autonomous nervous system can perpetuate the cycle of catecholamine cardiotoxicity, myocytolysis, and heart failure (93)(94)(95)(96)(97).…”

Section: Unified Neurogenic Theorymentioning

confidence: 93%

Pathogenesis of Chagas' Disease: Parasite Persistence and Autoimmunity

et al. 2011

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SUMMARY Acute Trypanosoma cruzi infections can be asymptomatic, but chronically infected individuals can die of Chagas' disease. The transfer of the parasite mitochondrial kinetoplast DNA (kDNA) minicircle to the genome of chagasic patients can explain the pathogenesis of the disease; in cases of Chagas' disease with evident cardiomyopathy, the kDNA minicircles integrate mainly into retrotransposons at several chromosomes, but the minicircles are also detected in coding regions of genes that regulate cell growth, differentiation, and immune responses. An accurate evaluation of the role played by the genotype alterations in the autoimmune rejection of self-tissues in Chagas' disease is achieved with the cross-kingdom chicken model system, which is refractory to T. cruzi infections. The inoculation of T. cruzi into embryonated eggs prior to incubation generates parasite-free chicks, which retain the kDNA minicircle sequence mainly in the macrochromosome coding genes. Crossbreeding transfers the kDNA mutations to the chicken progeny. The kDNA-mutated chickens develop severe cardiomyopathy in adult life and die of heart failure. The phenotyping of the lesions revealed that cytotoxic CD45, CD8 + γδ, and CD8α + T lymphocytes carry out the rejection of the chicken heart. These results suggest that the inflammatory cardiomyopathy of Chagas' disease is a genetically driven autoimmune disease.

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Pathology of intracardiac nerves in experimental Chagas disease

Abstract: Severe destruction of intrinsic cardiac nerves has been reported in experimental acute

Cited by 11 publications

References 20 publications

Effects of Cholinergic Stimulation with Pyridostigmine Bromide on Chronic Chagasic Cardiomyopathic Mice

Effects of Cholinergic Stimulation with Pyridostigmine Bromide on Chronic Chagasic Cardiomyopathic Mice

MHC class II antigen-expressing cells in cardiac ganglia of the rat

Pathogenesis of Chagas' Disease: Parasite Persistence and Autoimmunity

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