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Updated: Oct 22, 2025
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In Vivo Tracking of Edema Development and Microvascular Pathology in a Model of Experimental Cerebral Malaria Using Magnetic Resonance Imaging
Published on: June 8, 2017
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Using a new three-dimensional CUBIC tissue-clearing method to examine the brain during experimental cerebral malaria
Julia Matsuo-Dapaah1,2, Michelle Sue Jann Lee1, Ken J Ishii2,3,4,5
1Division of Malaria Immunology, Department of Microbiology and Immunology, Institute of Medical Science (IMSUT), University of Tokyo, Tokyo, Japan.
International Immunology
|August 29, 2021
Summary
Researchers used advanced 3D imaging to map Plasmodium parasites in mouse brains during experimental cerebral malaria (ECM). They found parasites preferentially accumulate in the olfactory bulb, offering new insights into disease mechanisms.
Area of Science:
- Neuroscience
- Immunology
- Parasitology
Background:
- Cerebral malaria (CM) is a severe complication of Plasmodium falciparum malaria, causing significant mortality.
- The exact molecular mechanisms of human CM are unclear, but parasite sequestration in cerebral vessels is implicated.
- Experimental cerebral malaria (ECM) models in mice, primarily driven by inflammation, have been considered distinct from human CM.
Purpose of the Study:
- To investigate the spatial distribution and sequestration of Plasmodium parasites within the whole-brain microvasculature during ECM.
- To apply and evaluate the CUBIC tissue-clearing method combined with light-sheet fluorescent microscopy (LSFM) for 3D visualization of ECM pathology.
Main Methods:
- Utilized CUBIC (Clear, Unobstructed, Brain/Body Imaging Cocktails and Computational analysis) tissue-clearing technique.
- Employed light-sheet fluorescent microscopy (LSFM) for whole-brain imaging.
- Reconstructed 3D images to analyze parasite distribution in microvessels during ECM.
Main Results:
- Demonstrated significantly higher accumulation of Plasmodium berghei ANKA (PbANKA) parasites in the olfactory bulb (OB) compared to other brain regions (cortex, cerebellum, brainstem).
- Observed preferential accumulation of PbANKA parasites in the brainstem when the OB was surgically removed, suggesting a role for the OB in initial parasite distribution.
Conclusions:
- The CUBIC tissue-clearing technology is effective for visualizing the entire brain and its microvasculature in ECM.
- This study provides novel insights into parasite distribution in ECM, potentially advancing our understanding of human cerebral malaria pathogenesis.
