Reduction of Experimental Cerebral Malaria and Its Related Proinflammatory Responses by the Novel Liposome-Based beta-Methasone Nanodrug
Web of Science
AuthorGuo, J; Waknine-Grinberg, JH; Mitchell, AJ; Barenholz, Y; Golenser, J
Source TitleBioMed Research International
University of Melbourne Author/sMitchell, Andrew
AffiliationChemical and Biomolecular Engineering
Document TypeJournal Article
CitationsGuo, J., Waknine-Grinberg, J. H., Mitchell, A. J., Barenholz, Y. & Golenser, J. (2014). Reduction of Experimental Cerebral Malaria and Its Related Proinflammatory Responses by the Novel Liposome-Based beta-Methasone Nanodrug. BIOMED RESEARCH INTERNATIONAL, 2014, https://doi.org/10.1155/2014/292471.
Access StatusOpen Access
Cerebral malaria (CM) is a severe complication of and a leading cause of death due to Plasmodium falciparum infection. CM is likely the result of interrelated events, including mechanical obstruction due to parasite sequestration in the microvasculature, and upregulation of Th1 immune responses. In parallel, blood-brain-barrier (BBB) breakdown and damage or death of microglia, astrocytes, and neurons occurs. We found that a novel formulation of a liposome-encapsulated glucocorticosteroid, β-methasone hemisuccinate (nSSL-BMS), prevents experimental cerebral malaria (ECM) in a murine model and creates a survival time-window, enabling administration of an antiplasmodial drug before severe anemia develops. nSSL-BMS treatment leads to lower levels of cerebral inflammation, expressed by altered levels of corresponding cytokines and chemokines. The results indicate the role of integrated immune responses in ECM induction and show that the new steroidal nanodrug nSSL-BMS reverses the balance between the Th1 and Th2 responses in malaria-infected mice so that the proinflammatory processes leading to ECM are prevented. Overall, because of the immunopathological nature of CM, combined immunomodulator/antiplasmodial treatment should be considered for prevention/treatment of human CM and long-term cognitive damage.
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