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Pathogenic Role of MicroParticles in Cerebral Malaria
Framework programme:
Project number:
EC contribution:
€ 998,327
24 months
Starting date:
1 October 2006

Keywords: Microparticles, endothelium, cerebral malaria, inflammation, immune activation, membrane vesiculation


Cerebral malaria (CM) remains a major public health problem worldwide. The main reason for this is our insufficient knowledge on the mechanisms leading to this complication. The partners of this consortium 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. This projects aims to unravel the mechanisms of MP production, delineate pharmacological ways to interfere with it, and to define the pathophysiological consequences of excessive MP production. It is expected that molecules relevant to the pathogenesis of this disease will be identified through broad spectrum of technologies including astrocytes and endothelial cell culture, flow cytometry, immunohistochemistry and membrane biology among others. This consortium brings together clinical and research teams working in complementary fields and developing specific approaches to tackle the questions being raised. Colleagues coming from countries which experience this endemic problem (including Malawi, Cameroon, Tanzania and India) play a major role in the project. Improving the understanding of CM pathogenesis should open new therapeutic avenues and in the long-term reduce malariaassociated mortality and morbidity by avoiding uncomplicated malaria to evolve in CM.

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