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Isolation and Analysis of Brain-sequestered Leukocytes from Plasmodium berghei ANKA-infected Mice
Published on: January 2, 2013
Plasmodium berghei ANKA Infection in ICR Mice as a Model of Cerebral Malaria
R Basir1, Ss Fazalul Rahiman, K Hasballah
1Department of Human Anatomy, Faculty of Medicine & Health Sciences, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia.
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 infection in inbred ICR mice as a model of cerebral malaria (CM).
Methods:
Infection in mice was initiated by intraperitoneal injection of 2 x 10(7) (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 important 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, pulmonary 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.
Insights
A new mouse model using Plasmodium berghei ANKA infection in ICR mice effectively mimics severe cerebral malaria (CM). This model aids in understanding CM pathogenesis by reproducing key pathological and clinical features of the disease.
Area of Science:
- Parasitology
- Immunology
- Pathology
Background:
- Animal models are crucial for studying malaria pathogenesis.
- Cerebral malaria (CM) is a severe complication of malaria requiring effective models for research.
Purpose of the Study:
- To establish and characterize a novel mouse model for cerebral malaria (CM) using Plasmodium berghei ANKA infection in inbred ICR mice.
Main Methods:
- Inbred ICR mice were infected intraperitoneally with Plasmodium berghei ANKA parasitized red blood cells.
- Clinical signs, parasitemia, organ pathology, and cytokine profiles were monitored.
Main Results:
- The model exhibited high parasitemia, mortality within 6-7 days, severe anemia, splenomegaly, and hepatomegaly.
- Histopathology revealed microvascular sequestration, Kupffer cell hyperplasia, pulmonary edema, and kidney hemorrhages, mirroring human CM.
- Elevated levels of proinflammatory (TNFα, IFNγ, IL-1, IL-6, IL-18) and anti-inflammatory (IL-10) cytokines were observed.
Conclusions:
- The Plasmodium berghei ANKA-infected ICR mouse model accurately reproduces key features of human cerebral malaria.
- This model serves as a valuable tool for advancing the understanding of CM pathogenesis and developing therapeutic strategies.

