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Failure of two distinct anti-apoptotic approaches to reduce mortality in experimental cerebral malaria.
Title | Failure of two distinct anti-apoptotic approaches to reduce mortality in experimental cerebral malaria. |
Publication Type | Journal Article |
Year of Publication | 2008 |
Authors | Helmers, AJ, Lovegrove, FE, Harlan, JM, Kain, KC, W Liles, C |
Journal | Am J Trop Med Hyg |
Volume | 79 |
Issue | 6 |
Pagination | 823-5 |
Date Published | 2008 Dec |
ISSN | 1476-1645 |
Keywords | Animals, Antimalarials, Apoptosis, ATP-Binding Cassette Transporters, Female, Gene Expression Regulation, Humans, Malaria, Cerebral, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, Oligopeptides, Plasmodium berghei, Proto-Oncogene Proteins c-bcl-2, Time Factors |
Abstract | Cerebral malaria is responsible for a high proportion of mortality in human Plasmodium falciparum infection. Previous studies have reported the presence of apoptosis in endothelial cells, astrocytes, neurons, and glial cells in experimental murine cerebral malaria caused by infection with Plasmodium berghei ANKA. Using this model, we tested two strategies, which have been shown to improve survival in murine models of sepsis: 1) treatment with z-VAD, a pancaspase inhibitor; and 2) overexpression of Bcl-2 using transgenic mice expressing human Bcl-2 (which prevents the release of apoptotic mediators from the mitochondria) from a myeloid cell promoter. Neither of these anti-apoptotic strategies, previously shown to provide therapeutic benefit in sepsis, improved survival in experimental cerebral malaria. |
Alternate Journal | Am. J. Trop. Med. Hyg. |
PubMed ID | 19052286 |