Dados do Trabalho

Título

Effect of soluble guanylate cyclase activator and stimulator on blood flow and survival in murine cerebral malaria by Plasmodium berghei ANKA

Introdução

Cerebral malaria (CM) is the major cause of death from Plasmodium falciparum infection. Susceptible mice infected with Plasmodium berghei ANKA develop a neurological syndrome similar to human CM, with brain microhemorrhages, blood cells adherent to the endothelium, endothelial dysfunction, low nitric oxide bioavailability, vasoconstriction and decreased cerebral blood flow (CBF).

Objetivo (s)

The present study analyzed the effect of riociguat and cinaciguat, respectively a stimulator and an activator of soluble guanylate cyclase (the nitric oxide target enzyme that signals for the vasodilation process) on CBF, permeability of the blood-brain barrier, survival, and cognitive impairment in animals with experimental CM (ECM).

Material e Métodos

The interventions were given on day 6 of infection, when the infected animals showed clinical signs of ECM. The animals were treated with one dose of riociguat and the antimalarial artemether or cinaciguat and artemether or vehicle and artemether and were analyzed after 1 hour or 6 hours. In survival experiments, animals with ECM were treated for 5 consecutive days with artemether, and in the first two also received a dose of riociguat or vehicle.

Resultados e Conclusão

In Laser Speckle with Contrast Imaging experiments, animals treated with riociguat and artemether showed increased CBF after 1 hour and 6 hours of treatment, whereas animals treated with vehicle and artemether had an increase only in the 1-hour treatment. Mice treated with cinaciguat and artemether showed no increase in CBF. Animals with ECM showed increased permeability of the blood-brain barrier to Evans blue dye and none of the treatments altered the permeability levels after 6 hours. Treatment with riociguat did not modify survival over vehicle treatment. Animals that recovered from ECM, treated with riociguat or vehicle, showed performance in behavioral tests similar to uninfected control animals. Conclusion: Riociguat was capable of sustaining an increase in CBF in the first 6 hours of treatment, but it did not confer benefits on the permeability of the blood-brain barrier, survival or cognition, and cinaciguat showed no beneficial effect in any of the analyzed parameters.

Palavras-chave

cerebral malaria, adjuvant therapy, sGC stimulator, sGC activator, vasoconstriction

Agradecimentos

CNPq, Faperj

Área

Eixo 06 | Protozooses