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Content archived on 2024-05-29

Pathogenic role of micro-vesiculation in cerebral Malaria

Objective

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 we propose 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, we want to identify the molecules that are relevant to pathogenesis.
Technologies implemented will include astrocytes and endothelial cell culture, flow cytometry, immunohistochemistry, membrane biology, magnetic resonance spectroscopy, neurochemistry, enzymology, proteomics and lipidomics. To this end we have brought together clinical and research teams that work in complementary fields and have a specific approach to tackle the different questions raised. Colleagues from endemic countries, including Malawi, Cameroon, Tanzania and India play a major role in the project. Our approach presents a high degree of interdisciplinarity, for the reason that our consortium involves experts in clinical practice, immunology, pathology, pathophysiology, cell biology, biochemistry and genetics. In each team, young researchers and students will work 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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Topic(s)

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Call for proposal

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FP6-2005-LIFESCIHEALTH-6
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Funding Scheme

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STREP - Specific Targeted Research Project

Coordinator

UNIVERSITÉ DE LA MÉDITERANNÉE, AIX MARSEILLE II
EU contribution
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Total cost

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Participants (7)

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