TRPV1 Contributes to Cerebral Malaria Severity and Mortality by Regulating Brain Inflammation. (16th May 2019)

• Record Type: Journal Article
• Authors: Pereira, Domingos Magno Santos; Teixeira, Simone Aparecida; Murillo, Oscar; Peixoto, Erika Paula Machado; Araújo, Mizael Calácio; Sousa, Nágila Caroline Fialho; Monteiro-Neto, Valério; Calixto, João Batista; Cunha, Thiago Mattar; Marinho, Cláudio Romero Farias; Muscará, Marcelo Nicolás; Fernandes, Elizabeth Soares
• Other Names: Isaguliants Maria Academic Editor.
• Is Part Of: Oxidative medicine and cellular longevity. Volume 2019(2019)
• Publication Date: 2019-05-16
• Subjects: Oxidative stress -- Periodicals; Cells -- Aging -- Periodicals; Cells -- Aging; Oxidative stress; Oxidative Stress -- Periodicals; Cell Aging -- Periodicals; Periodicals; 611.0181
• DOI: 10.1155/2019/9451671
• Languages: English
• ISSNs: 1942-0900

Abstract

Abstract : Transient receptor potential vanilloid 1 (TRPV1) is a Ca +2 -permeable channel expressed on neuronal and nonneuronal cells, known as an oxidative stress sensor. It plays a protective role in bacterial infection, and recent findings indicate that this receptor modulates monocyte populations in mice with malaria; however, its role in cerebral malaria progression and outcome is unclear. By using TRPV1 wild-type (WT) and knockout (KO) mice, the importance of TRPV1 to this cerebral syndrome was investigated. Infection with Plasmodium berghei ANKA decreased TRPV1 expression in the brain. Mice lacking TRPV1 were protected against Plasmodium -induced mortality and morbidity, a response that was associated with less cerebral swelling, modulation of the brain expression of endothelial tight-junction markers (junctional adhesion molecule A and claudin-5), increased oxidative stress (via inhibition of catalase activity and increased levels of H2 O2, nitrotyrosine, and carbonyl residues), and diminished production of cytokines. Plasmodium load was not significantly affected by TRPV1 ablation. Repeated subcutaneous administration of the selective TRPV1 antagonist SB366791 after malaria induction increased TRPV1 expression in the brain tissue and enhanced mouse survival. These data indicate that TRPV1 channels contribute to the development and outcome of cerebral malaria.