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Establishment of a murine model of cerebral malaria in KunMing mice infected with Plasmodium berghei ANKA

Published online by Cambridge University Press:  24 August 2016

YAN DING ,
WENYUE XU ,
TAOLI ZHOU ,
TAIPING LIU ,
HONG ZHENG  and
YONG FU
YAN DING
Affiliation:
Department of Pathogenic Biology, Third Military Medical University, 30 Gaotanyan Zhengjie, Shapingba District, Chongqing 400038, People's Republic of China
WENYUE XU
Affiliation:
Department of Pathogenic Biology, Third Military Medical University, 30 Gaotanyan Zhengjie, Shapingba District, Chongqing 400038, People's Republic of China
TAOLI ZHOU
Affiliation:
Department of Pathogenic Biology, Third Military Medical University, 30 Gaotanyan Zhengjie, Shapingba District, Chongqing 400038, People's Republic of China
TAIPING LIU
Affiliation:
Department of Pathogenic Biology, Third Military Medical University, 30 Gaotanyan Zhengjie, Shapingba District, Chongqing 400038, People's Republic of China
HONG ZHENG
Affiliation:
Department of Pathogenic Biology, Third Military Medical University, 30 Gaotanyan Zhengjie, Shapingba District, Chongqing 400038, People's Republic of China
YONG FU*
Affiliation:
Department of Pathogenic Biology, Third Military Medical University, 30 Gaotanyan Zhengjie, Shapingba District, Chongqing 400038, People's Republic of China
*
*Corresponding author: Department of Pathogenic Biology, Third Military Medical University, 30 Gaotanyan Zhengjie, Shapingba District, Chongqing 400038, People's Republic of China. E-mail: vincentfeu.tmmu@gmail.com
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Summary

Malaria remains one of the most devastating diseases. Cerebral malaria (CM) is a severe complication of Plasmodium falciparum infection resulting in high mortality and morbidity worldwide. Analysis of precise mechanisms of CM in humans is difficult for ethical reasons and animal models of CM have been employed to study malaria pathogenesis. Here, we describe a new experimental cerebral malaria (ECM) model with Plasmodium berghei ANKA infection in KunMing (KM) mice. KM mice developed ECM after blood-stage or sporozoites infection, and the development of ECM in KM mice has a dose-dependent relationship with sporozoites inoculums. Histopathological findings revealed important features associated with ECM, including accumulation of mononuclear cells and red blood cells in brain microvascular, and brain parenchymal haemorrhages. Blood–brain barrier (BBB) examination showed that BBB disruption was present in infected KM mice when displaying clinical signs of CM. In vivo bioluminescent imaging experiment indicated that parasitized red blood cells accumulated in most vital organs including heart, lung, spleen, kidney, liver and brain. The levels of inflammatory cytokines interferon-gamma, tumour necrosis factor-alpha, interleukin (IL)-17, IL-12, IL-6 and IL-10 were all remarkably increased in KM mice infected with P. berghei ANKA. This study indicates that P. berghei ANKA infection in KM mice can be used as ECM model to extend further research on genetic, pharmacological and vaccine studies of CM.

Keywords

cerebral malariamurine modelpathogenesisimmune responsePlasmodium berghei ANKAKM mice
Type
Research Article
Information
Parasitology , Volume 143 , Issue 12 , October 2016 , pp. 1672 - 1680
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Copyright
Copyright © Cambridge University Press 2016 

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