| Author | Moreira, Aline S. | |
| Author | Estato, Vanessa | |
| Author | Malvar, David C. | |
| Author | Sanches, Guilherme S. | |
| Author | Gomes, Fabiana | |
| Author | Tibiriçá, Eduardo | |
| Author | Daniel-Ribeiro, Cláudio Tadeu | |
| Author | Carvalho, Leonardo J. M. | |
| Access date | 2020-05-03T19:03:12Z | |
| Available date | 2020-05-03T19:03:12Z | |
| Document date | 2019 | |
| Citation | MOREIRA, Aline S. et al. L-arginine supplementation and thromboxane synthase inhibition increases cerebral blood fow in experimental cerebral malaria. Scientifc Reports, v. 9, p. 1-13, Sept. 2019. | pt_BR |
| ISSN | 2045-2322 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/41074 | |
| Language | eng | pt_BR |
| Publisher | Nature Research | pt_BR |
| Rights | open access | |
| Subject in Portuguese | Suplementação de L-arginina | pt_BR |
| Subject in Portuguese | Tromboxano sintase | pt_BR |
| Subject in Portuguese | Fluxo sanguíneo cerebral | pt_BR |
| Subject in Portuguese | Malária cerebral experimental | pt_BR |
| Subject in Portuguese | Inibição | pt_BR |
| Title | L-arginine supplementation and thromboxane synthase inhibition increases cerebral blood flow in experimental cerebral malaria | pt_BR |
| Type | Article | |
| DOI | 10.1038/s41598-019-49855-x | |
| Abstract | Cerebral malaria pathogenesis involves vascular dysfunction with low nitric oxide (NO) bioavailability, vasoconstriction and impaired vasodilation, leading to ischemia, tissue hypoxia and ultimately death. Cerebral blood flow (CBF) involves NO and other pathways, including arachidonic acid (AA)-derived metabolites. Here we show that mice with experimental cerebral malaria (ECM) by P. berghei ANKA showed marked decreases in CBF (as assessed by laser speckle contrast imaging - LSCI) and that administration of L-arginine supplementation (50 mg/kg) and/or of the thromboxane synthase inhibitor Ozagrel (100 mg/kg) induced immediate increases in CBF. L-arginine in combination with artesunate (32 mg/kg) induced immediate reversal of brain ischemia in the short-term (1 hour), but the effect subsided after 3 and 6 hours. Neither L-arginine nor Ozagrel reversed blood brain barrier breakdown. Mice with ECM showed brain levels of selected AA-derived metabolites with a vasoconstrictor profile, with increased levels of 8-isoprostanes, 20-HETE and 14,15-DHET, whereas mice infected with a non-ECM-inducing strain of P. berghei (NK65) showed a vasodilator profile, with normal levels of 20-HETE and 14,15-DHET and increased levels of PGE2. L-arginine is capable of partially reversing cerebral ischemia and AA metabolites may play a role in the cerebrovascular dysfunction in ECM. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa em Malária. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Universidade Federal Rural do Rio de Janeiro. Departamento de Ciências Fisiológicas. Seropédica, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa em Malária. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa em Malária. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Instituto Nacional de Cardiologia. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa em Malária. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa em Malária. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Subject | L-arginine supplementation | pt_BR |
| Subject | Thromboxane synthase | pt_BR |
| Subject | Inhibition | pt_BR |
| Subject | Cerebral blood fow | pt_BR |
| Subject | Experimental cerebral malaria | pt_BR |
