title: Simultaneously targeting inflammatory response and parasite sequestration in brain to treat Experimental Cerebral Malaria.
abstract: 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.
authors.affiliation: Department of Biochemistry, Indian Institute of Science, Bengaluru; 560012.
authors.forename: Chaitanya
authors.initials: C
authors.lastname: Dende
authors.affiliation: National Institute of Immunology, New Delhi; 110067, India.
authors.forename: Jairam
authors.initials: J
authors.lastname: Meena
authors.affiliation: National Institute of Immunology, New Delhi; 110067, India.
authors.forename: Perumal
authors.initials: P
authors.lastname: Nagarajan
authors.affiliation: National Institute of Immunology, New Delhi; 110067, India.
authors.forename: Amulya K
authors.initials: AK
authors.lastname: Panda
authors.affiliation: Department of Biochemistry, Indian Institute of Science, Bengaluru; 560012.
authors.forename: Pundi N
authors.initials: PN
authors.lastname: Rangarajan
authors.affiliation: Department of Biochemistry, Indian Institute of Science, Bengaluru; 560012.
authors.forename: Govindarajan
authors.initials: G
authors.lastname: Padmanaban
mesh_terms: D000818:Animals; D037621:Artemisinins / Q000627:therapeutic use; D001921:Brain / Q000469:parasitology*; D003474:Curcumin / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D004660:Encephalitis / Q000188:drug therapy; D004912:Erythrocytes / Q000187:drug effects / Q000469:parasitology*; D016779:Malaria, Cerebral / Q000188:drug therapy* / Q000469:parasitology; D051379:Mice; D010962:Plasmodium berghei / Q000187:drug effects*
chemical_list: D037621:Artemisinins; D003474:Curcumin; C055141:artemotil