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Updated: May 27, 2025
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
From Bench to Bedside: Unraveling Cerebral Malaria and Malarial Retinopathy by Combining Clinical and Pre-Clinical
Shannon McDonnell1, Ian J MacCormick2, Kevin Harkin1
1The Wellcome Wolfson Institute For Experimental Medicine, Queen's University Belfast, Belfast, UK.
Insights
Cerebral malaria (CM) and malarial retinopathy (MR) share pathological links. Comparing human and mouse models aids understanding of these neurovascular complications and informs new therapeutic strategies.
Area of Science:
- Neuroscience
- Infectious Diseases
- Ophthalmology
Background:
- Plasmodium falciparum infection causes cerebral malaria (CM), a severe neurovascular encephalopathy, particularly in children.
- Malarial retinopathy (MR), characterized by retinal hemorrhages and whitening, often accompanies CM and indicates blood retinal barrier (BRB) breakdown.
- The exact molecular mechanisms of CM and MR are not fully understood, but parasitemia drives inflammation and ischemia.
Purpose of the Study:
- To evaluate malarial retinopathy (MR) in clinical settings.
- To compare MR in humans with retinal pathology in the murine model of experimental CM (ECM).
- To elucidate the links between CM and MR for better understanding of disease pathogenesis and progression.
Main Methods:
- Review of clinical studies on CM and MR in human patients.
- Analysis of in vivo and post-mortem retinal studies in mouse models of experimental CM (ECM).
- Comparative evaluation of human and murine retinal findings in the context of CM and MR.
Main Results:
- Retinal examination in CM patients serves as a valuable tool for assessing pathology and predicting mortality/morbidity.
- The murine ECM model provides insights into brain pathology, but retinal aspects require further investigation.
- Comparative analysis highlights shared pathological features between human MR and ECM retinas.
Conclusions:
- Understanding the parallels between human CM/MR and experimental CM in mice is crucial for deciphering disease mechanisms.
- This comparative approach aids in developing novel therapeutic strategies for cerebral malaria and its ocular manifestations.
- Further research into the retina in ECM models will enhance our comprehension of CM pathogenesis.
Abstract:
Infection with Plasmodium falciparum carries a significant risk of cerebral malaria (CM). Children are particularly susceptible to human CM (HCM) which manifests as an acute neurovascular encephalopathy leading to high levels of mortality. Occurring in parallel with CM, malarial retinopathy (MR) is readily detected on ophthalmoscopy as one or more of: white-centered retinal hemorrhage, retinal whitening, and vessel discoloration. It leads to several distinct types of blood retinal barrier (BRB) breakdown. The precise molecular mechanisms underpinning CM and MR remain ill-defined, but parasitemia is known to drive progressive neurovascular obstruction and inflammation leading to cerebral and retinal edema and ischemia. Extensive clinical studies in patients with CM have shown that retinal examination is a useful approach for understanding pathology and an indicator for risk of mortality and morbidity. Fully understanding the cellular and molecular mechanisms that underpin CM and MR is important for developing new therapeutic approaches and in this regard the murine model of experimental CM (ECM) has proved to offer considerable value. Much is known about brain pathology in this model although much less is understood about the retina. In this review, we seek to evaluate MR in clinical scenarios and make comparisons with the retina from mice with ECM. Through detailed in vivo and post-mortem studies in the mouse and human retina, this review highlights the links between CM and MR and how this will aid our understanding of the disease progression and pathogenesis.
