A quantitative brain map of experimental cerebral malaria pathology
Patrick Strangward1, Michael J Haley1, Tovah N Shaw1
1Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom.
Plos Pathogens
|March 9, 2017
Summary
The murine experimental cerebral malaria model shares key pathological features with human cerebral malaria, including microvascular obstruction and vascular leakage, suggesting its utility for studying human disease mechanisms.
Area of Science:
- Neurology
- Immunology
- Pathology
Background:
- The murine model of experimental cerebral malaria (ECM) is widely used to study human cerebral malaria (HCM).
- However, the distinct etiologies of ECM and HCM have raised questions about the model's utility.
- This study provides the first detailed histopathological comparison of ECM and HCM.
Purpose of the Study:
- To determine the similarities and differences in the pathology of ECM and HCM.
- To assess the relevance of the ECM model for understanding HCM pathogenesis.
Main Methods:
- Spatial and quantitative histopathological assessment of the ECM syndrome.
- Analysis of parasitized red blood cell (pRBC) accumulation, immune cell infiltration, vascular leakage, and neuronal damage.
Main Results:
- Parasitized red blood cells (pRBCs) specifically occlude brain capillaries in ECM, similar to HCM.
- Cerebrovascular CD8+ T-cells co-localize with pRBCs, correlating with vascular leakage.
- Vascular leakage in ECM is not due to destruction but altered transport, mirroring HCM.
- Axonal injury and demyelination occur in ECM adjacent to vasculopathies, similar to HCM.
Conclusions:
- Despite differences in parasite accumulation, ECM and HCM share comparable cerebral pathologies.
- The ECM model, when used appropriately, can offer valuable mechanistic insights into HCM.
- This study validates the ECM model for specific aspects of human cerebral malaria research.
