title: Axonal injury in cerebral malaria.
abstract: Impairment of consciousness and other signs of cerebral dysfunction are common complications of severe Plasmodium falciparum malaria. Although the majority of patients make a complete recovery a significant minority, particularly children, have sequelae. The pathological process by which P. falciparum malaria induces severe but usually reversible neurological complications has not been elucidated. Impairment of transport within nerve fibers could induce neurological dysfunction and may have the potential either to resolve or to progress to irreversible damage. Beta-amyloid precursor protein (beta-APP) immunocytochemistry, quantified using digital image analysis, was used to detect defects in axonal transport in brain sections from 54 Vietnamese cases with P. falciparum malaria. The frequency and extent of beta-APP staining were more severe in patients with cerebral malaria than in those with no clinical cerebral involvement. Beta-APP staining was often associated with hemorrhages and areas of demyelination, suggesting that multiple processes may be involved in neuronal injury. The age of focal axonal damage, as determined by the extent of the associated microglial response, varied considerably within tissue sections from individual patients. These findings suggest that axons are vulnerable to a broad range of cerebral insults that occur during P. falciparum malaria infection. Disruption in axonal transport may represent a final common pathway leading to neurological dysfunction in cerebral malaria.
authors.affiliation: Nuffield Departments of Clinical Laboratory Sciences and Medicine, Level 5 Lab R 5501, The John Radcliffe Hospital, University of Oxford, Oxford, OX3 9DU, United Kingdom. isabelle.medana@ndcls.ox.ac.uk
authors.forename: Isabelle M
authors.initials: IM
authors.lastname: Medana
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: Day
authors.forename: Tran Tinh
authors.initials: TT
authors.lastname: Hien
authors.forename: Nguyen Thi Hoang
authors.initials: NT
authors.lastname: Mai
authors.forename: Delia
authors.initials: D
authors.lastname: Bethell
authors.forename: Nguyen Hoan
authors.initials: NH
authors.lastname: Phu
authors.forename: Jeremy
authors.initials: J
authors.lastname: Farrar
authors.forename: Margaret M
authors.initials: MM
authors.lastname: Esiri
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: White
authors.forename: Gareth D
authors.initials: GD
authors.lastname: Turner
mesh_terms: D000328:Adult; D016564:Amyloid beta-Protein Precursor / Q000032:analysis*; D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D001370:Axonal Transport; D001369:Axons / Q000737:chemistry / Q000473:pathology*; D001921:Brain / Q000473:pathology; D001923:Brain Chemistry; D002648:Child; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D006801:Humans; D016779:Malaria, Cerebral / Q000473:pathology*; D014744:Vietnam; D000097382:CD68 Molecule
chemical_list: D016564:Amyloid beta-Protein Precursor; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D005904:Glial Fibrillary Acidic Protein; C067980:CD68 antigen, human; D000097382:CD68 Molecule