Document Detail


Nitric oxide protection against murine cerebral malaria is associated with improved cerebral microcirculatory physiology.
MedLine Citation:
PMID:  21415018     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Pedro Cabrales; Graziela M Zanini; Diana Meays; John A Frangos; Leonardo J M Carvalho
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-03-16
Journal Detail:
Title:  The Journal of infectious diseases     Volume:  203     ISSN:  1537-6613     ISO Abbreviation:  J. Infect. Dis.     Publication Date:  2011 May 
Date Detail:
Created Date:  2011-04-19     Completed Date:  2011-06-30     Revised Date:  2013-06-30    
Medline Journal Info:
Nlm Unique ID:  0413675     Medline TA:  J Infect Dis     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1454-63     Citation Subset:  AIM; IM    
Affiliation:
La Jolla Bioengineering Institute, La Jolla, CA 92037, USA.
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MeSH Terms
Descriptor/Qualifier:
Alkenes / pharmacology*
Animals
Cerebral Hemorrhage / prevention & control
Cerebrum / blood supply*
Hemodynamics / drug effects
Inflammation / prevention & control
Malaria, Cerebral / metabolism,  parasitology,  prevention & control*
Mice
Mice, Inbred C57BL
Microcirculation / drug effects*
Nitric Oxide / metabolism*
Plasmodium berghei
Vasoconstriction / drug effects
Grant Support
ID/Acronym/Agency:
R01 AI082610-01/AI/NIAID NIH HHS; R01 AI082610-03/AI/NIAID NIH HHS; R01 HL087290-04/HL/NHLBI NIH HHS; R01-AI082610/AI/NIAID NIH HHS; R01-HL087290/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Alkenes; 0/dipropylenetriamine-NONOate; 10102-43-9/Nitric Oxide
Comments/Corrections

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