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https://www.arca.fiocruz.br/handle/icict/33940
Type
ArticleCopyright
Open access
Embargo date
2020-07-10
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- INI - Artigos de Periódicos [3392]
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NITRIC OXIDE PROTECTION AGAINST MURINE CEREBRAL MALARIA IS ASSOCIATED WITH IMPROVED CEREBRAL MICROCIRCULATORY PHYSIOLOGY
Affilliation
La Jolla Bioengineering Institute. San Diego, CA, USA / University of California, San Diego. Department of Bioengineering. San Diego, CA, USA.
La Jolla Bioengineering Institute. San Diego, CA, USA / Fundação Oswaldo Cruz. Instituto de Pesquisas Clinicas Evandro Chagas. Serviço de Parasitologia. Rio de Janeiro, RJ, Brasil.
La Jolla Bioengineering Institute. San Diego, CA, USA.
La Jolla Bioengineering Institute. San Diego, CA, USA
La Jolla Bioengineering Institute. San Diego, CA, USA
La Jolla Bioengineering Institute. San Diego, CA, USA / Fundação Oswaldo Cruz. Instituto de Pesquisas Clinicas Evandro Chagas. Serviço de Parasitologia. Rio de Janeiro, RJ, Brasil.
La Jolla Bioengineering Institute. San Diego, CA, USA.
La Jolla Bioengineering Institute. San Diego, CA, USA
La Jolla Bioengineering Institute. San Diego, CA, USA
Abstract
Cerebral malaria (CM) is a leading cause of death in Plasmodium falciparum infections. In the Plasmodium berghei ANKA (PbA) murine model, CM pathogenesis is associated with low nitric oxide (NO) bioavailability and brain microcirculatory complications, with a marked decrease in cerebral blood flow, vasoconstriction, vascular plugging by adherent cells, and hemorrhages. Using intravital microscopy through a closed cranial window, here we show that NO supplementation in the form of a NO donor (dipropylenetriamine NONOate [DPTA-NO]) prevented vasoconstriction and improved blood flow in pial vessels of PbA-infected mice. Arterioles and venules of smaller diameters (20-35.5 μm) showed better response to treatment than vessels of larger diameters (36-63 μm). Exogenous NO provided protection against brain hemorrhages (mean, 1.4 vs 24.5 hemorrhagic foci per section) and inflammation (mean, 2.5 vs 10.9 adherent leukocytes per 100 μm vessel length) compared with saline treatment. In conclusion, NO protection against CM is associated with improved brain microcirculatory hemodynamics and decreased vascular pathology.
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