Inhibition of hypoxia-associated response and kynurenine production in response to hyperbaric oxygen as mechanisms involved in protection against experimental cerebral malaria.

摘要: Cerebral malaria (CM) is a multifactorial syndrome involving an exacerbated proinflammatory status, endothelial cell activation, coagulopathy, hypoxia, and accumulation of leukocytes parasites in the brain microvasculature. Despite significant improvements control, 15% mortality still observed CM cases, 25% survivors develop neurologic sequelae for life-even after appropriate antimalarial therapy. A treatment that ameliorates clinical signs, resulting complete healing, urgently needed. Previously, we showed hyperbaric oxygen (HBO)-protective effect against experimental CM. Here, provide molecular evidence HBO targets cells by decreasing their activation inhibits parasite leukocyte accumulation, thus improving cerebral microcirculatory blood flow. increased expression aryl hydrocarbon receptor over hypoxia-inducible factor 1-α (HIF-1α), oxygen-sensitive cytosolic receptor, along with decreased indoleamine 2,3-dioxygenase 1 kynurenine levels. Moreover, ablation HIF-1α mice conferred protection improved survival. We propose should be pursued as adjunctive therapy patients to prolong survival diminish deleterious reaction. Furthermore, our data support use therapeutic strategies improve outcomes non-CM disorders affecting brain.-Bastos, M. F., Kayano, A. C. V., Silva-Filho, J. L., Dos-Santos, K., Judice, C., Blanco, Y. Shryock, N., Sercundes, Ortolan, L. S., Francelin, Leite, A., Oliveira, R., Elias, R. M., Câmara, N. O. Lopes, S. P., Albrecht, Farias, Vicente, Werneck, Giorgio, Verinaud, Epiphanio, Marinho, Lalwani, Amino, Aliberti, J., Costa, F. T. Inhibition hypoxia-associated response production mechanisms involved malaria.