Plasmodium berghei ANKA Infection in ICR Mice as a Model of Cerebral Malaria

Abstract

Background: Animal models with various combination of host-parasite have long been employed to study malaria pathogenesis. Here, we describe the combination of Plasmodium berghei ANKA infec- tion in inbred ICR mice as a model of cerebral malaria (CM). Methods: Infection in mice was initiated by intraperitoneal injection of 2 x 107 (0.2ml) parasitized red blood cells (PRBCs). Results: This model can produce a severe degree of infection presented by the high degree of parasitaemia followed by death 6-7 days post infection. Severe anemia, splenomegaly, hepatomegaly and discolourations of major organs were observed. Histopathological findings revealed several i m- portant features mimicking human CM including, microvascular sequestration of PRBCs in major organs, particularly in the brain, hypertrophy and hyperplasia of the kupffer cells in the liver, pulmo- nary edema and hyaline membrane formation in the lungs and haemorrhages in the kidney’s medulla and cortex. Proinflammatory cytokines TNFα, IFNγ, IL-1, IL-6 and IL-18, and anti-inflammatory cytokine IL-10 were all found to be elevated in the plasma of infected mice. Conclusion: This model can reproduce many of the important features of CM and therefore can be used as a tool to advance our understanding of the disease pathogenesis.

Keywords

• Animal model
• Malaria
• Plasmodium berghei
• ICR mice