Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/33945
Title: Murine cerebral malaria is associated with a vasospasm-like microcirculatory dysfunction, and survival upon rescue treatment is markedly increased by nimodipine
Authors: Cabrales, Pedro
Zanini, Graziela M.
Meays, Diana
Frangos, John A.
Carvalho, Leonardo J. M.
Affilliation: La Jolla Bioengineering Institute. San Diego, CA, USA.
La Jolla Bioengineering Institute. San Diego, CA, USA / Fundação Oswaldo Cruz. Instituto de Pesquisa Clínica Evandro Chagas. 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: Brain hemodynamics in cerebral malaria (CM) is poorly understood, with apparently conflicting data showing microcirculatory hypoperfusion and normal or even increased blood flow in large arteries. Using intravital microscopy to assess the pial microvasculature through a closed cranial window in the murine model of CM by Plasmodium berghei ANKA, we show that murine CM is associated with marked decreases (mean: 60%) of pial arteriolar blood flow attributable to vasoconstriction and decreased blood velocity. Leukocyte sequestration further decreased perfusion by narrowing luminal diameters in the affected vessels and blocking capillaries. Remarkably, vascular collapse at various degrees was observed in 44% of mice with CM, which also presented more severe vasoconstriction. Coadministration of artemether and nimodipine, a calcium channel blocker used to treat postsubarachnoid hemorrhage vasospasm, to mice presenting CM markedly increased survival compared with artemether plus vehicle only. Administration of nimodipine induced vasodilation and increased pial blood flow. We conclude that vasoconstriction and vascular collapse play a role in murine CM pathogenesis and nimodipine holds potential as adjunctive therapy for CM.
Keywords: Murine cerebral malaria
Vasospasm
Microcirculatory dysfunction
Nimodipine
Issue Date: 2010
Publisher: Elsevier
Citation: CABRALES, Pedro et al. Murine cerebral malaria is associated with a vasospasm-like microcirculatory dysfunction, and survival upon rescue treatment is markedly increased by nimodipine. American Journal of Pathology, v. 176, n. 3, Mar. 2010.
DOI: 10.2353/ajpath.2010.090691
ISSN: 0002-9440
Copyright: restricted access
Appears in Collections:INI - Artigos de Periódicos




FacebookTwitterDeliciousLinkedInGoogle BookmarksBibTex Format mendeley Endnote DiggMySpace

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