RESUMO
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.
Assuntos
Cardiomiopatias/tratamento farmacológico , Doença de Chagas/tratamento farmacológico , Doença Crônica/tratamento farmacológico , Brometo de Piridostigmina/uso terapêutico , Animais , Cardiomiopatias/metabolismo , Doença de Chagas/metabolismo , Inibidores da Colinesterase/uso terapêutico , Eletrocardiografia , Frequência Cardíaca/efeitos dos fármacos , Interferon gama/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Trypanosoma cruzi/patogenicidadeRESUMO
The aim of the present study was to evaluate the effects of changes to the autonomic nervous system in mice during the acute phase of Chagas disease, which is an infection caused by the parasite Trypanosoma cruzi. The following types of mice were inoculated with T. cruzi (CHG): wild-type (WT) and vesicular acetylcholine transporter knockdown (KDVAChT) C57BL/6j mice; wild-type non-treated (NT) FVB mice; FVB mice treated with pyridostigmine bromide (PYR) or salbutamol (SALB); and ß(2)-adrenergic receptor knockout (KOß2) FVB mice. During infection and at 18-21 days after infection (acute phase), the survival curves, parasitaemia, electrocardiograms, heart rate variability, autonomic tonus and histopathology of the animals were evaluated. Negative control groups were matched for age, genetic background and treatment. The KDVAChT-CHG mice exhibited a significant shift in the electrocardiographic, autonomic and histopathological profiles towards a greater inflammatory immune response that was associated with a reduction in blood and tissue parasitism. In contrast, the CHG-PYR mice manifested reduced myocardial inflammation and lower blood and tissue parasitism. Similar results were observed in CHG-SALB animals. Unexpectedly, the KOß2-CHG mice exhibited less myocardial inflammation and higher blood and tissue parasitism, which were associated with reduced mortality. These findings could have been due to the increase in vagal tone observed in the KOß2 mice, which rendered them more similar to the CHG-PYR animals. In conclusion, our results indicate a marked immunomodulatory role for the parasympathetic and sympathetic autonomic nervous systems, which inhibit both the inflammatory immune response and parasite clearance during the acute phase of experimental Chagas heart disease in mice.
Assuntos
Doença de Chagas/imunologia , Doença de Chagas/fisiopatologia , Inflamação/imunologia , Inflamação/fisiopatologia , Sistema Nervoso Parassimpático/fisiopatologia , Sistema Nervoso Simpático/fisiopatologia , Doença Aguda , Animais , Atenolol/farmacologia , Doença de Chagas/metabolismo , Doença de Chagas/parasitologia , Eletrocardiografia/métodos , Frequência Cardíaca/efeitos dos fármacos , Frequência Cardíaca/fisiologia , Inflamação/metabolismo , Inflamação/parasitologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Miocárdio/metabolismo , Miocárdio/patologia , Parasitemia/imunologia , Parasitemia/metabolismo , Parasitemia/parasitologia , Parasitemia/fisiopatologia , Sistema Nervoso Parassimpático/efeitos dos fármacos , Sistema Nervoso Parassimpático/imunologia , Sistema Nervoso Parassimpático/metabolismo , Propranolol/farmacologia , Brometo de Piridostigmina/farmacologia , Receptores Adrenérgicos beta 2/metabolismo , Sistema Nervoso Simpático/efeitos dos fármacos , Sistema Nervoso Simpático/imunologia , Sistema Nervoso Simpático/metabolismoRESUMO
Parkinson's disease patients experience motor signs and non-motor symptoms caused by the disease. Deep brain stimulation of the Subthalamic Nucleus (STN) itself or its ventral or dorsal borders is one of the treatment options indicated to treat the refractory symptoms of this disease. However, it is still unknown which edge, when stimulated, generates more beneficial effects for these patients, which is the objective of this systematic review. To answer this question, electronic and manual searches were conducted in five databases and gray literature to identify studies that answered the question in this review. The selection of studies, data extraction, and analysis of the risk of bias of the included studies were performed. In total, seven studies were included in this systematic review. Most studies presented a minimal risk of bias, and their main methodological limitation was related to the sample inclusion criteria. Stimulation of the dorsal or ventral borders of the STN resulted in improved motor signs of Parkinson's disease, with some of the studies tending towards the choice of dorsal border stimulation for better motor effects, while the improvement in non-motor symptoms and inhibitory control was due to stimulation of the ventral border. The findings of this systematic review suggest that the improvement in the motor signs of Parkinson's disease can be brought about by stimulating the dorsal or ventral borders of the subthalamic nucleus, whereas non-motor symptoms such as anxiety improve with stimulation of the ventral border.