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MPCM Résumé de rapport

Project ID: 37749
Financé au titre de: FP6-LIFESCIHEALTH
Pays: France

Final Report Summary - MPCM (Pathogenic role of MicroVesiculation in Cerebral Malaria)

Cerebral malaria (CM) remains a major problem of public health worldwide. The main reason is our insufficient knowledge on the mechanisms leading to this complication. We recently showed that the production of microparticles (MP) is dramatically elevated in patients with CM. Evidence in a murine model indicates that MP may be a pivotal element in CM pathogenesis, and in vitro data on human brain microvascular endothelial cells suggest that reducing MP production by anti-inflammatory drugs correlates with a reduced cytoadherence of parasitised erythrocytes.

Therefore, the MPCM project aimed to unravel the mechanisms of MP production, to delineate pharmacological ways to interfere with it, and to define the pathophysiological consequences of excessive MP production. Starting from the patient who develops CM, towards the fine composition of MP, the project aimed to identify the molecules that are relevant to pathogenesis. Technologies implemented included astrocytes and endothelial cell culture, flow cytometry, immunohistochemistry, membrane biology, magnetic resonance spectroscopy, neurochemistry, enzymology, proteomics and lipidomics.

To this end, the project brought together clinical and research teams that worked in complementary fields and have a specific approach to tackle the different questions raised. Colleagues from endemic countries, including Malawi, Cameroon, Tanzania and India played a major role in the project. The approach presented a high degree of interdisciplinarity, which is why the consortium involved experts in clinical practice, immunology, pathology, pathophysiology, cell biology, biochemistry and genetics.

In each team, young researchers and students worked in close relationship with experienced researchers. A better understanding of CM pathogenesis should open new therapeutic avenues and lead to a better handling of patients, reduced malaria-associated mortality and morbidity by avoiding uncomplicated malaria to evolve in CM.

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