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Updated: Aug 8, 2026
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
Endothelin in a murine model of cerebral malaria
Fabiana S Machado1, Mahalia S Desruisseaux, Nagajyothi
1Department of Medical and Molecular Parasitology, New York University School of Medicine, New York, New York 10016, USA.
Insights
Cerebral malaria (CM) involves brain inflammation and reduced blood flow. This study found increased endothelin-1 (ET-1) and related molecules in mice with experimental CM, suggesting a role in disease pathology.
Area of Science:
- Neuroscience
- Immunology
- Pathology
Background:
- Cerebral malaria (CM) is a severe complication of Plasmodium falciparum infection, particularly dangerous for children.
- Pathogenesis of CM involves brain inflammation, glial cell activation, and vascular changes.
- Previous research showed reduced cerebral blood flow in a mouse model of CM.
Purpose of the Study:
- To investigate the potential role of endothelin-1 (ET-1) in the pathogenesis of experimental cerebral malaria (ECM).
- To examine the expression of ET-1 and its related components in the brains of mice infected with Plasmodium berghei ANKA (PbA).
Main Methods:
- Used reverse transcription-polymerase chain reaction (RT-PCR) and quantitative real-time PCR to analyze gene expression.
- Examined brains of C57BL/6 mice infected with PbA on Day 5.
- Assessed expression of ET-1, endothelin converting enzyme (ECE), and endothelin receptors A and B (ET(A), ET(B)).
- Performed histopathology to evaluate microglial cell morphology and clustering.
Main Results:
- Markedly increased ET-1 and ECE mRNA expression observed via RT-PCR in PbA-infected mice.
- Quantitative PCR revealed a 3-fold increase in ET-1 and significant upregulation of ET(A) and ET(B) receptors.
- Histopathology showed microglial cell activation and clustering in infected mice.
Conclusions:
- The study demonstrates a significant increase in ET-1 and its associated components in a murine model of CM.
- These findings suggest a role for ET-1 in the vasculopathy and immunopathology characteristic of CM.
- Further research is needed to fully elucidate the impact of ET-1 on CM progression.
Abstract:
Cerebral malaria (CM) remains a deadly complication of Plasmodium falciparum infection, and children are at high risk of developing encephalopathy as a result of CM. This is probably a consequence of the activation of many of the inflammatory cytokines as well as the glial cells and the vascular endothelium in the brain. We have previously demonstrated that there is a striking reduction in cerebral blood flow by magnetic resonance imaging when mice are infected with Plasmodium berghei ANKA (PbA), and we now demonstrate a possible role for endothelin (ET-1) in the pathogenesis of CM. The brains of female C57BL/6 mice with PbA infection were examined at Day 5 for the expression of ET-1, endothelin converting enzyme (ECE), and the endothelin receptors A and B (ET(A) and ET(B)) by both reverse transcription-polymerase chain reaction (RT-PCR) and quantitative real-time PCR. ET-1 and ECE mRNA expression was markedly increased by RT-PCR in PbA-infected mice. Real-time quantitative PCR demonstrated a 3-fold increase in ET-1 (P < 0.05) and a significant increase in ET(A) and ET(B) expression (P < 0.05) in PbA-infected mice. Histopathology bof PbA-infected mice demonstrated a transformation in the morphology of microglial cells and clustering of these cells consistent with activation. Though the full impact of ET-1 on CM remains to be elucidated, these findings demonstrate that in the murine model, there is a significant increase in ET-1 and its components, which is associated with the vasculopathy and immunopathology of CM.
