Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/30455
Title: Cognitive dysfunction is sustained after rescue therapy in experimental cerebral malaria, and is reduced by additive antioxidant therapy
Authors: Reis, Patricia A.
Comim, Clarissa M.
Hermani, Fernanda
Silva, Bruno
Barichello, Tatiana
Portella, Aline C.
Gomes, Flavia C. A.
Sab, Ive M.
Frutuoso, Valber S.
Oliveira, Marcus F.
Bozza, Patricia T.
Bozza, Fernando A.
Dal-Pizzol, Felipe
Zimmerman, Guy A.
Quevedo, João
Faria Neto, Hugo C. Castro
Affilliation: Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.
Universidade do Extremo Sul Catarinense. Instituto Nacional de Ciência e Tecnologia Translacional em Medicina. Laboratório de Neurociências. Criciúma, SC, Brasil.
Universidade do Extremo Sul Catarinense. Instituto Nacional de Ciência e Tecnologia Translacional em Medicina. Laboratório de Neurociências. Criciúma, SC, Brasil.
Universidade do Extremo Sul Catarinense. Instituto Nacional de Ciência e Tecnologia Translacional em Medicina. Laboratório de Neurociências. Criciúma, SC, Brasil.
Universidade do Extremo Sul Catarinense. Instituto Nacional de Ciência e Tecnologia Translacional em Medicina. Laboratório de Neurociências. Criciúma, SC, Brasil.
Universidade Federal do Rio de Janeiro. Instituto de Ciências Biomédicas. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio de Janeiro. Instituto de Ciências Biomédicas. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio de Janeiro. Instituto de Bioquímica Médica. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto de Pesquisa Clínica Evandro Chagas. Rio de Janeiro, RJ, Brasil.
Universidade do Extremo Sul Catarinense. Laboratório de Fisiopatologia Experimental. Criciúma, SC, Brasil.
University of Utah. Department of Medicine. Program in Human Molecular Biology and Genetics. Salt Lake City, Utah, USA.
Universidade do Extremo Sul Catarinense. Instituto Nacional de Ciência e Tecnologia Translacional em Medicina. Laboratório de Neurociências. Criciúma, SC, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.
Abstract: Neurological impairments are frequently detected in children surviving cerebral malaria (CM), the most severe neurological complication of infection with Plasmodium falciparum. The pathophysiology and therapy of long lasting cognitive deficits in malaria patients after treatment of the parasitic disease is a critical area of investigation. In the present study we used several models of experimental malaria with differential features to investigate persistent cognitive damage after rescue treatment. Infection of C57BL/6 and Swiss (SW) mice with Plasmodium berghei ANKA (PbA) or a lethal strain of Plasmodium yoelii XL (PyXL), respectively, resulted in documented CM and sustained persistent cognitive damage detected by a battery of behavioral tests after cure of the acute parasitic disease with chloroquine therapy. Strikingly, cognitive impairment was still present 30 days after the initial infection. In contrast, BALB/c mice infected with PbA, C57BL6 infected with Plasmodium chabaudi chabaudi and SW infected with non lethal Plasmodium yoelii NXL (PyNXL) did not develop signs of CM, were cured of the acute parasitic infection by chloroquine, and showed no persistent cognitive impairment. Reactive oxygen species have been reported to mediate neurological injury in CM. Increased production of malondialdehyde (MDA) and conjugated dienes was detected in the brains of PbA-infected C57BL/6 mice with CM, indicating high oxidative stress. Treatment of PbA-infected C57BL/6 mice with additive antioxidants together with chloroquine at the first signs of CM prevented the development of persistent cognitive damage. These studies provide new insights into the natural history of cognitive dysfunction after rescue therapy for CM that may have clinical relevance, and may also be relevant to cerebral sequelae of sepsis and other disorders.
Keywords: Cognitive Dysfunction
Experimental Cerebral Malaria
Additive Antioxidant Therapy
Rescue Therapy
keywords: Disfunção cognitiva
Malária cerebral experimental
terapia antioxidante aditiva
terapia de resgate
Issue Date: 2010
Publisher: Public Library of Science
Citation: REIS, Patricia A. et al. Cognitive Dysfunction Is Sustained after Rescue Therapy in Experimental Cerebral Malaria, and Is Reduced by Additive Antioxidant Therapy. PLoS Pathog., v.6, n.6, e1000963, 16p, June 2010.
DOI: 10.1371/journal.ppat.1000963
ISSN: 1553-7366
Copyright: open access
Appears in Collections:IOC - Artigos de Periódicos

Files in This Item:
File Description SizeFormat 
patriciareis_vfrutuoso_etal_IOC_2010.pdf3.8 MBAdobe PDFView/Open


FacebookTwitterDeliciousLinkedInGoogle BookmarksBibTex Format mendeley Endnote DiggMySpace

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.