Axonal injury in cerebral malaria.
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.
Medana
Isabelle M
IM
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
Day
Nicholas P
NP
Hien
Tran Tinh
TT
Mai
Nguyen Thi Hoang
NT
Bethell
Delia
D
Phu
Nguyen Hoan
NH
Farrar
Jeremy
J
Esiri
Margaret M
MM
White
Nicholas J
NJ
Turner
Gareth D
GD
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
D016564:Amyloid beta-Protein Precursor; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D005904:Glial Fibrillary Acidic Protein; C067980:CD68 antigen, human; D000097382:CD68 Molecule