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. 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, 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, via the definition of the fine composition of MP using appropriate models both animal and in vitro, we expect to be able to identify molecules relevant to the pathogenesis of this disease. To achieve this goal we will implement a broad spectrum of technologies including astrocytes and endothelial cell culture, flow cytometry, immunohistochemistry, membrane biology, magnetic resonance spectroscopy, neurochemistry, enzymology, proteomics and lipidomics.
This consortium brought together clinical and research teams working in complementary fields and developing specific approaches to tackle the raised questions. Colleagues from endemic countries, including Malawi, Cameroon, Tanzania and India play a major role in the project. The project presents a high degree of interdisciplinarity, since the 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 senior investigators to implement acquisition of expertise.
In fine, the better understanding of CM pathogenesis foreseen by this project should open new therapeutic avenues and, in the long term, help to better handle patients and to reduce malaria-associated mortality and morbidity by avoiding uncomplicated malaria to evolve in CM.
Source: project website
