Nisimura Lindice Mitie, Estato Vanessa, de Souza Elen Mello, Reis Patricia A, Lessa Marcos Adriano, Castro-Faria-Neto Hugo Caire, Pereira Mirian Claudia de Souza, Tibiriçá Eduardo, Garzoni Luciana Ribeiro
Laboratório de Investigação Cardiovascular, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Rio de Janeiro, Brazil.
Laboratório de Morfologia e Morfogênese Viral, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Rio de Janeiro, Brazil.
PLoS Negl Trop Dis. 2014 Jul 10;8(7):e2998. doi: 10.1371/journal.pntd.0002998. eCollection 2014 Jul.
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.
心肌病是恰加斯病（CD）的主要临床形式；然而，也可能出现脑部表现，如脑膜脑炎、缺血性中风和认知障碍。本研究的目的是调查急性恰加斯病小鼠大脑中的功能性微血管改变和氧化应激。用克氏锥虫（T. cruzi）Y株诱导瑞士韦伯斯特小鼠（SWM）患上急性恰加斯病。在15天的时间里，使用活体视频显微镜分析脑功能毛细血管密度（自发灌注毛细血管的数量）、白细胞滚动和黏附以及微血管内皮依赖性反应。我们还使用硫代巴比妥酸反应性物质（TBARS）法评估了脑氧化应激。与未感染组相比，急性恰加斯病显著诱导了脑功能性微血管改变，包括：（i）功能性毛细血管稀疏；（ii）白细胞滚动和黏附增加；（iii）微血管血小板 - 白细胞聚集体形成；（iv）内皮对乙酰胆碱反应的改变。此外，感染动物的脑氧化应激增加。我们得出结论，小鼠急性恰加斯病诱导了脑微血管病，其特征为灌注毛细血管发生率降低、大量微血管血小板 - 白细胞聚集体、白细胞与内皮相互作用显著增加以及与氧化应激相关的脑小动脉内皮功能障碍。这些结果表明脑微循环改变参与了恰加斯病的神经学表现。
