I. M. MedanaN. P. DayT. T. HienN. T.H. MaiD. BethellN. H. PhuG. D. TurnerJ. FarrarN. J. WhiteM. M. EsiriNuffield Department of Clinical MedicineChurchill HospitalMahidol UniversityUCLOxford University Clinical Research UnitUniversity of OxfordJohn Radcliffe Hospital2018-08-242018-08-242007-04-01Neuropathology and Applied Neurobiology. Vol.33, No.2 (2007), 179-19213652990030518462-s2.0-33847713791https://repository.li.mahidol.ac.th/handle/123456789/24938Disruption 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.Mahidol UniversityMedicineNeuroscienceArticleSCOPUS10.1111/j.1365-2990.2006.00777.x