Further evidence for an anti-inflammatory role of artesunate in experimental cerebral malaria

Malaria Journal

Research

Daniel Cisalpino¹  Danielle G Souza¹  Milene A Rachid²  David H Rodrigues³  Natália P Rocha³  Alline C Campos⁴  Fátima Brant⁴  Fabiana S Machado⁴  Aline S Miranda⁴  Antônio L Teixeira Jr⁵ 

[1] Department of Microbiology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil;Department of Pathology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil;Laboratório de Imunofarmacologia, Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, Av. Antônio Carlos, 6627, Pampulha, 31270-901, Belo Horizonte, Brazil;Programme in Health Sciences: Infectious Diseases and Tropical Medicine, School of Medicine, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil;Laboratório de Imunofarmacologia, Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, Av. Antônio Carlos, 6627, Pampulha, 31270-901, Belo Horizonte, Brazil;Programme in Health Sciences: Infectious Diseases and Tropical Medicine, School of Medicine, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil;Laboratório de Imunofarmacologia, Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, Av. Antônio Carlos, 6627, Pampulha, 31270-901, Belo Horizonte, Brazil;Laboratory of Medical Investigation, School of Medicine, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil;

关键词: Malaria;    Cerebral malaria;    Memory impairment;    Artesunate;    Cytokines;    Neuroinflammation;   

DOI  :  10.1186/1475-2875-12-388

 received in 2013-08-18, accepted in 2013-10-29,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundCerebral malaria (CM) is a clinical syndrome resulting from Plasmodium falciparum infection. A wide range of clinical manifestations follow the disease including cognitive dysfunction, seizures and coma. CM pathogenesis remains incompletely understood and without treatment this condition is invariably fatal. Artesunate has been accepted as the most effective drug for treating severe malaria. Besides its antiparasitic activity, an anti-inflammatory property has also been reported. In the current study, the immunomodulatory role of artesunate was investigated using a Plasmodium berghei ANKA model of CM, trough evaluation of behavioural changes and cytokines expression in hippocampus and in frontal cortex.MethodsC57Bl/6 mice were infected with P. berghei by intraperitoneal route, using a standardized inoculation of 106 parasitized erythrocytes. Memory function was evaluated using the step-down inhibitory avoidance test. The mRNA expression of IFN-γ, IL-1β, IL-6 and TNF in the frontal cortex and hippocampus of control and infected mice on day 5 post-infection were estimated by quantitative real time PCR. Plasmodium berghei -infected mice also received intraperitoneally a single dose of artesunate (32 mg/kg) on day 4 post-infection, and 24 hours after treatment behavioural and immunological analysis were performed. The protein levels of cytokines IL-2, IL-6, IL-10, IL-17, IFN-γ, TNF in the serum, frontal cortex and hippocampus of controls and P. berghei -infected mice treated or not treated with artesunate were determined using a cytometric bead array (CBA) kit. The survival and neurological symptoms of CM were also registered.ResultsCM mice presented a significant impairment of aversive memory compared to controls on day 5 post-infection. A higher mRNA expression of pro-inflammatory cytokines was found in the hippocampus and frontal cortex of infected mice. A single dose of artesunate was also able to decrease the expression of inflammatory cytokines in the hippocampus and frontal cortex of P. berghei-infected mice. In parallel, a significant improvement in neurological symptoms and survival were observed in artesunate treated mice.ConclusionsIn summary, the current study provided further evidence that CM affects key brain areas related to cognition process. In addition, different patterns of cytokine expression during the course of CM could be modulated by a single administration of the anti-malarial artesunate.

【 授权许可】

CC BY   
© Miranda et al.; licensee BioMed Central Ltd. 2013