Cargando…
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...
Autores principales: | , , , , , |
---|---|
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 |
_version_ | 1782383762805358592 |
---|---|
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. |
format | Online Article Text |
id | pubmed-4521148 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT dendechaitanya simultaneouslytargetinginflammatoryresponseandparasitesequestrationinbraintotreatexperimentalcerebralmalaria AT meenajairam simultaneouslytargetinginflammatoryresponseandparasitesequestrationinbraintotreatexperimentalcerebralmalaria AT nagarajanperumal simultaneouslytargetinginflammatoryresponseandparasitesequestrationinbraintotreatexperimentalcerebralmalaria AT pandaamulyak simultaneouslytargetinginflammatoryresponseandparasitesequestrationinbraintotreatexperimentalcerebralmalaria AT rangarajanpundin simultaneouslytargetinginflammatoryresponseandparasitesequestrationinbraintotreatexperimentalcerebralmalaria AT padmanabangovindarajan simultaneouslytargetinginflammatoryresponseandparasitesequestrationinbraintotreatexperimentalcerebralmalaria |