Journal
PROGRESS IN NEUROBIOLOGY
Volume 91, Issue 2, Pages 140-151Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pneurobio.2010.01.007
Keywords
Cerebral malaria; Cell-cell interactions; Microparticles; Endothelium
Categories
Funding
- National Health and Medical Research Council of Australia (NHMRC) [464893, 512469]
- Australian Research Council (ARC) [DP0774425]
- European Union-National Health and Medical Research Council of Australia (EU-NHMRC) [512101, 512691]
- Sir Zelman Cowen Universities Fund
- Rebecca Cooper Foundation
- University of Sydney
- Australian Research Council [DP0774425] Funding Source: Australian Research Council
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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. (C) 2010 Elsevier Ltd. All rights reserved.
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