Publication: Cerebral calpain in fatal falciparum malaria
Issued Date
2007-04-01
Resource Type
ISSN
13652990
03051846
03051846
Other identifier(s)
2-s2.0-33847713791
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Mahidol University
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SCOPUS
Bibliographic Citation
Neuropathology and Applied Neurobiology. Vol.33, No.2 (2007), 179-192
Suggested Citation
I. M. Medana, N. P. Day, T. T. Hien, N. T.H. Mai, D. Bethell, N. H. Phu, G. D. Turner, J. Farrar, N. J. White, M. M. Esiri Cerebral calpain in fatal falciparum malaria. Neuropathology and Applied Neurobiology. Vol.33, No.2 (2007), 179-192. doi:10.1111/j.1365-2990.2006.00777.x Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/24938
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Title
Cerebral calpain in fatal falciparum malaria
Abstract
Disruption of axonal transport may represent a final common pathway leading to neurological dysfunction in cerebral malaria (CM). Calpains are calcium (Ca2+)-activated cysteine proteases which have been implicated in axonal injury in neurological diseases of various aetiologies. In this study we examined the association between μ- and m-calpain, the specific inhibitor calpastatin, and axonal injury in post mortem brain tissue from patients who died from severe malaria. Calpains were associated with axons labelled for the β-amyloid precursor protein that detects impaired axonal transport. Elevated levels of calpastatin were rarely observed in injured axons. There were increased numbers of neurones with μ-calpain in the nuclear compartment in severe malaria cases compared with non-neurological controls, and increased numbers of glia with nuclear μ-calpain in CM patients compared with non-CM malaria cases and non-neurological controls. There was marked redistribution of calpastatin in the sequestered Plasmodium falciparum-infected erythrocytes. Responses specific to malaria infection were ascertained following analysis of brain samples from fatal cases with acute axonal injury, HIV encephalitis, and progressive multifocal leucoencephalopathy. Our findings implicate a role for calpains in the modulation of disease progression in CM. © 2006 Blackwell Publishing Ltd.