| Author | Marin, Adriana A. | |
| Author | Murillo, Oscar | |
| Author | Sussmann, Rodrigo A. | |
| Author | Ortolan, Luana S. | |
| Author | Battagello, Daniela S. | |
| Author | Quirino, Thatyane de Castro | |
| Author | Bittencourt, Jackson C. | |
| Author | Epiphanio, Sabrina | |
| Author | Katzin, Alejandro M. | |
| Author | Carvalho, Leonardo J. M. | |
| Access date | 2021-10-06T10:59:07Z | |
| Available date | 2021-10-06T10:59:07Z | |
| Document date | 2021 | |
| Citation | MARIN, Adriana A. et al. Perillyl Alcohol Reduces Parasite Sequestration and Cerebrovascular Dysfunction during Experimental Cerebral Malaria. Antimicrobial Agents and Chemotherapy, v. 64, n. 5, e00004-21, 14 p, May 2021. | pt_BR |
| ISSN | 1098-6596 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/49289 | |
| Language | eng | pt_BR |
| Publisher | American Society for Microbiology | pt_BR |
| Rights | restricted access | |
| Subject in Portuguese | Plasmodium berghei | pt_BR |
| Subject in Portuguese | Malária cerebral experimental | pt_BR |
| Subject in Portuguese | Disfunção vascular | pt_BR |
| Subject in Portuguese | Álcool perillyl | pt_BR |
| Subject in Portuguese | Terapia preventiva | pt_BR |
| Subject in Portuguese | Imunomodulação | pt_BR |
| Title | Perillyl Alcohol Reduces Parasite Sequestration and Cerebrovascular Dysfunction during Experimental Cerebral Malaria | pt_BR |
| Type | Article | |
| DOI | 10.1128/AAC.00004-21 | |
| Abstract | Cerebral malaria (CM) is a severe immune vasculopathy which presents
a high mortality rate (15 to 20%), despite the availability of artemisinin-based therapy.
More effective immunomodulatory and/or antiparasitic therapies are urgently
needed. Experimental cerebral malaria (ECM) in mice is used to elucidate aspects
involved in this pathology because it manifests many of the neurological features
of CM. In the present study, we evaluated the potential mechanisms involved in
the protection afforded by perillyl alcohol (POH) in mouse strains susceptible to
CM caused by Plasmodium berghei ANKA (PbA) infection through intranasal preventive
treatment. Additionally, we evaluated the interaction of POH with the cerebral
endothelium using an in vitro model of human brain endothelial cells (HBEC).
Pharmacokinetic approaches demonstrated constant and prolonged levels of POH
in the plasma and brain after a single intranasal dose. Treatment with POH effectively
prevented vascular dysfunction. Furthermore, treatment with POH reduced
the endothelial cell permeability and PbA parasitized red blood cells in the brain
and spleen. Finally, POH treatment decreased the accumulation of macrophages
and T and B cells in the spleen and downregulated the expression of endothelial
adhesion molecules (ICAM-1, VCAM-1, and CD36) in the brain. POH is a potent
monoterpene that prevents cerebrovascular dysfunction in vivo and in vitro,
decreases parasite sequestration, and modulates different processes related to the
activation, permeability, and integrity of the blood-brain barrier (BBB), thereby preventing
cerebral edema and inflammatory infiltrates. | pt_BR |
| Affilliation | Universidade de São Paulo. Instituto de Ciências Biomédicas. Departamento de Parasitologia. São Paulo, SP, Brasil. | pt_BR |
| Affilliation | Universidade de São Paulo. Instituto de Ciências Biomédicas. Departamento de Parasitologia. São Paulo, SP, Brasil. | pt_BR |
| Affilliation | Universidade de São Paulo. Instituto de Ciências Biomédicas. Departamento de Parasitologia. São Paulo, SP, Brasil. | pt_BR |
| Affilliation | Universidade de São Paulo. Instituto de Ciências Biomédicas. Departamento de Imunologia. São Paulo, SP, Brasil. | pt_BR |
| Affilliation | Universidade de São Paulo. Instituto de Ciências Biomédicas. Departamento de Anatomia. São Paulo, SP, Brasil. | pt_BR |
| Affilliation | Universidade de São Paulo. Faculdade de Ciências Farmacêuticas. Departamento de Análises Clínicas e Toxicológicas. São Paulo, SP, Brasil. | pt_BR |
| Affilliation | Universidade de São Paulo. Instituto de Ciências Biomédicas. Departamento de Anatomia. São Paulo, SP, Brasil. | pt_BR |
| Affilliation | Universidade de São Paulo. Faculdade de Ciências Farmacêuticas. Departamento de Análises Clínicas e Toxicológicas. São Paulo, SP, Brasil. | pt_BR |
| Affilliation | Universidade de São Paulo. Instituto de Ciências Biomédicas. Departamento de Parasitologia. São Paulo, SP, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Insituto Oswaldo Cruz. Laboratório de Pesquisa em Malária. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Subject | Plasmodium berghei | pt_BR |
| Subject | Experimental cerebral malaria | pt_BR |
| Subject | Vascular dysfunction | pt_BR |
| Subject | Perillyl alcohol | pt_BR |
| Subject | Preventive therapy | pt_BR |
| Subject | Immunomodulation | pt_BR |
| Embargo date | 2023 | |
