title: Cerebral malaria -- a neurovascular pathology with many riddles still to be solved.
abstract: Cerebral malaria (CM), one of the most common fatal complications of the heterogenous syndrome named severe malaria, is indubitably a post-infectious neurovascular pathology, as evidenced by histopathological analyses. This neurological syndrome is characterised not only by the cytoadherence of Plasmodium falciparum-infected erythrocytes, but also by morphological and functional alterations of brain microvascular endothelial cells subsequent to their interactions with circulating cells, such as platelets, monocytes, lymphocytes, and dendritic cells. During CM, host cells, in particular immune cells, are found recruited and activated at the site of sequestration, where they release various soluble molecules. Among these, cytokines play a major role in CM pathogenesis. Indeed, cerebral complications appear to be due to an imbalance between pro-inflammatory and anti-inflammatory mediators. Cytokines (notably interferon-gamma, tumour necrosis factor, lymphotoxin) and chemokine receptors (notably CCR5) are also responsible for blood-brain barrier alterations and biochemical changes leading to the brain parenchymal lesions that can be observed in CM. In return, glial cells can influence blood-borne elements, and thereby worsen the pathology. Numerous problems remain to be solved, especially the sequence of pathological events, namely the order in which the circulating cells sequester on the endothelial wall. A better understanding of the molecular mechanisms involved in CM pathogenesis is needed if we are capable of preventing cerebral complications and improving the quality of patient management.
authors.affiliation: Experimental Parasitology Unit, IFR48, Faculty of Medicine, Université de la Méditerranée, F-13385 Marseille Cedex 5, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Coltel
authors.forename: Valéry
authors.initials: V
authors.lastname: Combes
authors.forename: Nicholas H
authors.initials: NH
authors.lastname: Hunt
authors.forename: Georges E
authors.initials: GE
authors.lastname: Grau
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000473:pathology; D001921:Brain / Q000098:blood supply / Q000473:pathology; D004730:Endothelium, Vascular / Q000473:pathology; D006801:Humans; D016779:Malaria, Cerebral / Q000097:blood / Q000473:pathology* / Q000503:physiopathology*