Inhibition of hypoxia‐associated response and kynurenine production in response to hyperbaric oxygen as mechanisms involved in protection against experimental cerebral malaria
| Autor: | Stefanie C. P. Lopes, Pritesh Lalwani, Nathaniel Shryock, João Luiz Silva-Filho, Rafaella Oliveira, Letusa Albrecht, Rogerio Amino, Carla C. Judice, Alessandro S. Farias, João Conrado Khouri Dos-Santos, Sabrina Epiphanio, Fabio T. M. Costa, Liana Verinaud, Cristina P. Vicente, Julio Aliberti, Rosa Maria Elias, Luana dos Santos Ortolan, Ana Carolina A. V. Kayano, Michelle Klein Sercundes, Niels Olsen Saraiva Câmara, Carolina Francelin, Juliana A. Leite, Claudio Romero Farias Marinho, Selma Giorgio, Marcele F. Bastos, Claudio C. Werneck, Yara C. Blanco |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Malaria Cerebral Pharmacology Biochemistry Microcirculation Proinflammatory cytokine Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Genetics medicine Coagulopathy Animals Hypoxia Molecular Biology Kynurenine Hyperbaric Oxygenation biology business.industry Research Brain Endothelial Cells Hypoxia (medical) Hypoxia-Inducible Factor 1 alpha Subunit medicine.disease Aryl hydrocarbon receptor Mice Inbred C57BL Oxygen Endothelial stem cell 030104 developmental biology chemistry Cerebral Malaria Cerebrovascular Circulation biology.protein Female METABÓLITOS medicine.symptom business 030217 neurology & neurosurgery Biotechnology |
| Zdroj: | Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP |
| ISSN: | 1530-6860 0892-6638 |
| DOI: | 10.1096/fj.201700844r |
| Popis: | Cerebral malaria (CM) is a multifactorial syndrome involving an exacerbated proinflammatory status, endothelial cell activation, coagulopathy, hypoxia, and accumulation of leukocytes and parasites in the brain microvasculature. Despite significant improvements in malaria control, 15% of mortality is still observed in CM cases, and 25% of survivors develop neurologic sequelae for life-even after appropriate antimalarial therapy. A treatment that ameliorates CM clinical signs, resulting in complete healing, is urgently needed. Previously, we showed a hyperbaric oxygen (HBO)-protective effect against experimental CM. Here, we provide molecular evidence that HBO targets brain endothelial cells by decreasing their activation and inhibits parasite and leukocyte accumulation, thus improving cerebral microcirculatory blood flow. HBO treatment increased the expression of aryl hydrocarbon receptor over hypoxia-inducible factor 1-α (HIF-1α), an oxygen-sensitive cytosolic receptor, along with decreased indoleamine 2,3-dioxygenase 1 expression and kynurenine levels. Moreover, ablation of HIF-1α expression in endothelial cells in mice conferred protection against CM and improved survival. We propose that HBO should be pursued as an adjunctive therapy in CM patients to prolong survival and diminish deleterious proinflammatory reaction. Furthermore, our data support the use of HBO in therapeutic strategies to improve outcomes of non-CM disorders affecting the brain.-Bastos, M. F., Kayano, A. C. A. V., Silva-Filho, J. L., Dos-Santos, J. C. K., Judice, C., Blanco, Y. C., Shryock, N., Sercundes, M. K., Ortolan, L. S., Francelin, C., Leite, J. A., Oliveira, R., Elias, R. M., Câmara, N. O. S., Lopes, S. C. P., Albrecht, L., Farias, A. S., Vicente, C. P., Werneck, C. C., Giorgio, S., Verinaud, L., Epiphanio, S., Marinho, C. R. F., Lalwani, P., Amino, R., Aliberti, J., Costa, F. T. M. Inhibition of hypoxia-associated response and kynurenine production in response to hyperbaric oxygen as mechanisms involved in protection against experimental cerebral malaria. |
| Databáze: | OpenAIRE |
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