Nitric Oxide Protection Against Murine Cerebral Malaria Is Associated With Improved Cerebral Microcirculatory Physiology

• Published in: The Journal of infectious diseases 2011-05, Vol.203 (10), p.1454-1463
• Main Authors: Cabrales, Pedro, Zanini, Graziela M., Meays, Diana, Frangos, John A., Carvalho, Leonardo J. M.
• Format: Article
• Language: English
• Subjects: Alkenes - pharmacology; Animals; Arterioles; Biological and medical sciences; Blood flow; Blood vessels; Cerebral Hemorrhage - prevention & control; Cerebral malaria; Cerebrum - blood supply; Fundamental and applied biological sciences. Psychology; Hemodynamics - drug effects; Hemorrhage; Human protozoal diseases; Infections; Infectious diseases; Inflammation - prevention & control; Leukocytes; Major and Brief Reports; Malaria; Malaria, Cerebral - metabolism; Malaria, Cerebral - parasitology; Malaria, Cerebral - prevention & control; Medical sciences; Mice; Mice, Inbred C57BL; Microbiology; Microcirculation - drug effects; Nitric Oxide - metabolism; Oxides; PARASITES; Parasitic diseases; Plasmodium berghei; Protozoal diseases; Vasoconstriction - drug effects; Venules
• ISSN: 0022-1899; 1537-6613; 0022-1899; 1537-6613
• DOI: 10.1093/infdis/jir058

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.