title: Microvesiculation and cell interactions at the brain-endothelial interface in cerebral malaria pathogenesis.
abstract: Cerebral malaria (CM) is still a major world health problem whose pathogenic mechanisms remain incompletely understood. After reviewing some particularities of anti-malarial immunity, we focus here on the neurovascular aspects of CM. We specifically address the central role of endothelial activation and alteration in disease pathogenesis. We discuss the respective roles of "mediator-induced" versus "host cell-induced" mechanisms of endothelial alteration. The former include cytokines, chemokines and their receptors, while the latter encompass cells located inside and outside the vessel, notably glial cells. We also present evidence for a pathogenic role for membrane microparticles (MP) in CM, based on studies in African patients and in a recognised mouse model. Intervention studies on MP production, via either gene knockout or pharmacological inhibition, can prevent the neurological syndrome and its associated mortality, suggesting potential new therapeutic avenues.
authors.affiliation: Department of Pathology, Vascular Immunology Unit, Sydney Medical School, The University of Sydney, Australia.
authors.forename: Valéry
authors.initials: V
authors.lastname: Combes
authors.forename: Fatima
authors.initials: F
authors.lastname: El-Assaad
authors.forename: Dorothée
authors.initials: D
authors.lastname: Faille
authors.forename: Ronan
authors.initials: R
authors.lastname: Jambou
authors.forename: Nicholas H
authors.initials: NH
authors.lastname: Hunt
authors.forename: Georges E R
authors.initials: GE
authors.lastname: Grau
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000276:immunology*; D001921:Brain / Q000276:immunology*; D016207:Cytokines / Q000276:immunology*; D004730:Endothelium, Vascular / Q000276:immunology*; D006801:Humans; D016779:Malaria, Cerebral / Q000276:immunology*; D051379:Mice; D008959:Models, Neurological; D013572:Synaptic Vesicles / Q000276:immunology*
chemical_list: D016207:Cytokines