title: The role of cerebral oedema in the pathogenesis of cerebral malaria.
abstract: It has been suggested that sequestration of parasitized red blood cells might contribute to the pathogenesis of cerebral malaria (CM), by hypoxia causing either: (i) compensatory vasodilatation with a resultant increase in the brain volume; or (ii) enhancing cytokine-induced nitric oxide (NO) production via induction of inducible NO synthase (iNOS). Available evidence suggests that cerebral oedema is the initiating and probably the most important factor in the pathogenesis of murine CM. The relevance of this model in the study of the pathogenesis of CM has been questioned. However, a closer look at published reports on both human and murine CM, in this review, suggests that the pathogenesis of the murine model of CM might reflect more closely the CM seen in African children than that seen in Asian adults. It is also proposed that the role of iNOS induction during CM is protective: that the primary purpose of iNOS induction is to inhibit the side effects of brain indoleamine 2,3-dioxygenase (IDO) induction and quinolinic acid accumulation during hypoxia.
authors.affiliation: Division of Parasitology, National Institute for Medical Research, London, UK. lsanni@nimr.mrc.ac.uk
authors.forename: L A
authors.initials: LA
authors.lastname: Sanni
mesh_terms: D000328:Adult; D000349:Africa; D000818:Animals; D001210:Asia, Southeastern; D001812:Blood-Brain Barrier; D001929:Brain Edema / Q000209:etiology / Q000503:physiopathology*; D002448:Cell Adhesion; D002560:Cerebrovascular Circulation; D002648:Child; D016207:Cytokines / Q000502:physiology; D004734:Energy Metabolism; D006801:Humans; D020925:Hypoxia-Ischemia, Brain / Q000209:etiology / Q000503:physiopathology; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D008288:Malaria / Q000150:complications / Q000503:physiopathology; D016779:Malaria, Cerebral / Q000209:etiology*; D016778:Malaria, Falciparum / Q000150:complications / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008954:Models, Biological; D009243:NAD / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D010962:Plasmodium berghei; D017378:Quinolinic Acid / Q000378:metabolism; D014366:Tryptophan Oxygenase / Q000378:metabolism; D014664:Vasodilation
chemical_list: D016207:Cytokines; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D009419:Nerve Tissue Proteins; D009243:NAD; D009569:Nitric Oxide; D014366:Tryptophan Oxygenase; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D017378:Quinolinic Acid