Characterization of cerebral malaria in the outbred Swiss Webster mouse infected by Plasmodium berghei ANKA
Characterization of cerebral malaria in the outbred Swiss Webster mouse infected by Plasmodium berghei ANKA
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DOI：
10.1111/j.1365-2613.2008.00622.x
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发表时间：
2009-04-01
影响因子：
3
通讯作者：
de Moura Carvalho, Leonardo Jose
中科院分区：
文献类型：
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作者：
Martins, Yuri Chaves;Smith, Mary Jane;de Moura Carvalho, Leonardo Jose
伯氏疟原虫(PBA)感染易感近交系小鼠是研究脑型疟疾发病机制最常用的实验模型。事实上，使用这种模型的工作已经提出了许多与这种并发症相关的机制的概念，尽管近交系代表了几个优点，并且在大多数研究中都表明了这一点，但近交系模型的使用在一些方法中可以显示出独特的用处，例如精细的后数量性状基因定位和发现与CM易感性或耐药性相关的基因，以及药理学和疫苗研究。在这里，我们描述了PBA感染和CM发病率的特征，并描述了与之相关的多器官病理在杂交的瑞士Webster小鼠中的特征。该模型显示了相当大的(62.7%)和可重复性的CM发生率，表现为临床体征和脑组织病理改变(微出血、水肿和单核细胞堵塞血管)。肺、肝、胸腺和脾也出现了与近交系相似的主要病理变化。寄生虫血症水平与发生CM的风险相关，感染6-7天寄生虫血症数值较高的小鼠的风险明显更高。这种远缘繁殖的CM模型适用于针对这种疟疾并发症的遗传、疫苗和药物研究。
Plasmodium berghei ANKA (PbA) infection in susceptible inbred mouse strains is the most commonly used experimental model to study pathogenesis of cerebral malaria (CM). Indeed, many concepts on mechanisms related to this complication have arisen from works using this model, Although inbred strains present several advantages and are indicated for most studies, the use of outbred models can show unique usefulness in a number of approaches such as fine post-quantitative trait loci mapping and discovery of genes relevant to CM susceptibility or resistance, as well as pharmacological and vaccine studies. Here we describe the features of PbA infection and CM incidence, and characterize the associated multiorgan pathology in the outbred Swiss Webster mouse. This model showed a sizeable (62.7%) and reproducible incidence of CM demonstrated by clinical signs and histopathological changes in brain (microhaemorrhages, oedema and vessel plugging by mononuclear cells). Major pathological changes were also observed in lungs, liver, thymus and spleen, analogous to those observed in inbred strains. Parasitaemia levels were associated with the risk of CM development, the risk being significantly higher in mice showing higher values of parasitaemia on days 6-7 of infection. This outbred CM model is then suitable for genetic, vaccine and drug studies targeting this malaria complication.