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Simultaneously targeting inflammatory response and parasite sequestration in brain to treat Experimental Cerebral Malaria

Malaria afflicts around 200 million people annually, with a mortality number close to 600,000. The mortality rate in Human Cerebral Malaria (HCM) is unacceptably high (15–20%), despite the availability of artemisinin-based therapy. An effective adjunct therapy is urgently needed. Experimental Cerebr...

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Autores principales: Dende, Chaitanya, Meena, Jairam, Nagarajan, Perumal, Panda, Amulya K., Rangarajan, Pundi N., Padmanaban, Govindarajan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4521148/
https://www.ncbi.nlm.nih.gov/pubmed/26227888
http://dx.doi.org/10.1038/srep12671
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author Dende, Chaitanya
Meena, Jairam
Nagarajan, Perumal
Panda, Amulya K.
Rangarajan, Pundi N.
Padmanaban, Govindarajan
author_facet Dende, Chaitanya
Meena, Jairam
Nagarajan, Perumal
Panda, Amulya K.
Rangarajan, Pundi N.
Padmanaban, Govindarajan
author_sort Dende, Chaitanya
collection PubMed
description Malaria afflicts around 200 million people annually, with a mortality number close to 600,000. The mortality rate in Human Cerebral Malaria (HCM) is unacceptably high (15–20%), despite the availability of artemisinin-based therapy. An effective adjunct therapy is urgently needed. Experimental Cerebral Malaria (ECM) in mice manifests many of the neurological features of HCM. Migration of T cells and parasite-infected RBCs (pRBCs) into the brain are both necessary to precipitate the disease. We have been able to simultaneously target both these parameters of ECM. Curcumin alone was able to reverse all the parameters investigated in this study that govern inflammatory responses, CD8(+) T cell and pRBC sequestration into the brain and blood brain barrier (BBB) breakdown. But the animals eventually died of anemia due to parasite build-up in blood. However, arteether-curcumin (AC) combination therapy even after the onset of symptoms provided complete cure. AC treatment is a promising therapeutic option for HCM.
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spelling pubmed-45211482015-08-05 Simultaneously targeting inflammatory response and parasite sequestration in brain to treat Experimental Cerebral Malaria Dende, Chaitanya Meena, Jairam Nagarajan, Perumal Panda, Amulya K. Rangarajan, Pundi N. Padmanaban, Govindarajan Sci Rep Article Malaria afflicts around 200 million people annually, with a mortality number close to 600,000. The mortality rate in Human Cerebral Malaria (HCM) is unacceptably high (15–20%), despite the availability of artemisinin-based therapy. An effective adjunct therapy is urgently needed. Experimental Cerebral Malaria (ECM) in mice manifests many of the neurological features of HCM. Migration of T cells and parasite-infected RBCs (pRBCs) into the brain are both necessary to precipitate the disease. We have been able to simultaneously target both these parameters of ECM. Curcumin alone was able to reverse all the parameters investigated in this study that govern inflammatory responses, CD8(+) T cell and pRBC sequestration into the brain and blood brain barrier (BBB) breakdown. But the animals eventually died of anemia due to parasite build-up in blood. However, arteether-curcumin (AC) combination therapy even after the onset of symptoms provided complete cure. AC treatment is a promising therapeutic option for HCM. Nature Publishing Group 2015-07-31 /pmc/articles/PMC4521148/ /pubmed/26227888 http://dx.doi.org/10.1038/srep12671 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Dende, Chaitanya
Meena, Jairam
Nagarajan, Perumal
Panda, Amulya K.
Rangarajan, Pundi N.
Padmanaban, Govindarajan
Simultaneously targeting inflammatory response and parasite sequestration in brain to treat Experimental Cerebral Malaria
title Simultaneously targeting inflammatory response and parasite sequestration in brain to treat Experimental Cerebral Malaria
title_full Simultaneously targeting inflammatory response and parasite sequestration in brain to treat Experimental Cerebral Malaria
title_fullStr Simultaneously targeting inflammatory response and parasite sequestration in brain to treat Experimental Cerebral Malaria
title_full_unstemmed Simultaneously targeting inflammatory response and parasite sequestration in brain to treat Experimental Cerebral Malaria
title_short Simultaneously targeting inflammatory response and parasite sequestration in brain to treat Experimental Cerebral Malaria
title_sort simultaneously targeting inflammatory response and parasite sequestration in brain to treat experimental cerebral malaria
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4521148/
https://www.ncbi.nlm.nih.gov/pubmed/26227888
http://dx.doi.org/10.1038/srep12671
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