Abstract
Cardiomyopathy is the main clinical form of Chagas disease (CD); however, cerebral manifestations, such as meningoencephalitis, ischemic stroke and cognitive impairment, can also occur. The aim of the present study was to investigate functional microvascular alterations and oxidative stress in the brain of mice in acute CD. Acute CD was induced in Swiss Webster mice (SWM) with the Y strain of Trypanosoma cruzi (T. cruzi). Cerebral functional capillary density (the number of spontaneously perfused capillaries), leukocyte rolling and adhesion and the microvascular endothelial-dependent response were analyzed over a period of fifteen days using intravital video-microscopy. We also evaluated cerebral oxidative stress with the thiobarbituric acid reactive species TBARS method. Compared with the non-infected group, acute CD significantly induced cerebral functional microvascular alterations, including (i) functional capillary rarefaction, (ii) increased leukocyte rolling and adhesion, (iii) the formation of microvascular platelet-leukocyte aggregates, and (iv) alteration of the endothelial response to acetylcholine. Moreover, cerebral oxidative stress increased in infected animals. We concluded that acute CD in mice induced cerebral microvasculopathy, characterized by a reduced incidence of perfused capillaries, a high number of microvascular platelet-leukocyte aggregates, a marked increase in leukocyte-endothelium interactions and brain arteriolar endothelial dysfunction associated with oxidative stress. These results suggest the involvement of cerebral microcirculation alterations in the neurological manifestations of CD.
Highlights
Chagas disease (CD), which is caused by the protozoan Trypanosoma cruzi (T. cruzi), is endemic in Latin America and affects approximately 10 million people worldwide [1]
Chagas disease (CD) is a neglected tropical illness caused by the parasite Trypanosoma cruzi (T. cruzi)
Meningoencephalitis occurs in children with acute CD and in immunosuppressed patients suffering acute CD reactivation
Summary
Chagas disease (CD), which is caused by the protozoan Trypanosoma cruzi (T. cruzi), is endemic in Latin America and affects approximately 10 million people worldwide [1]. During acute CD, the peripheral inflammatory response is characterized by the presence of macrophages [10], NK cells [11] and intense lymphocyte polyclonal activation [12] This response is followed by the systemic synthesis of pro-inflammatory cytokines [13], nitric oxide (NO) [14] and reactive oxygen species [15]. Microvascular alterations have been implicated in the pathogenesis of Chagas cardiomyopathy and include vascular constrictions, microaneurysms, dilatations and platelet aggregation, resulting in the formation of transient occlusive thrombi. These alterations contribute to myocytolytic necrosis followed by inflammatory infiltration and interstitial fibrosis. Vasoactive substances, including endothelin-1 and thromboxane, are involved in the modulation of vascular responses during T. cruzi infection, contributing to platelet aggregation, microvascular spasms and endothelial dysfunction [16]
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