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Neuropathogenesis of canine visceral leishmaniasis: investigation of inflammatory mediators

Grant number: 12/10415-0
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): August 01, 2012
Effective date (End): June 30, 2015
Field of knowledge:Agronomical Sciences - Veterinary Medicine - Animal Pathology
Principal researcher:Gisele Fabrino Machado
Grantee:Guilherme Dias de Melo
Home Institution: Faculdade de Medicina Veterinária (FMVA). Universidade Estadual Paulista (UNESP). Campus de Araçatuba. Araçatuba , SP, Brazil
Associated scholarship(s):14/03078-3 - Neuropathogenesis of experimental visceral leishmaniasis: investigation of parasite migration and immune response in a murine model, BE.EP.DR


Visceral leishmaniasis (VL) is an anthropozoonosis with worldwide distribution, and in Brazil it is caused by the protozoan Leishmania chagasi. The disease affects mainly the organs with mononuclear phagocyte system cells, such as spleen, lymph nodes, bone marrow, liver, besides skin. As occurs in other protozoan diseases, the peripherical infection by L. chagasi also promotes central nervous system (CNS) alterations, and in dogs with VL there are reports of meningitis, choroiditis, anti-Leishmania antibodies in the cerebrospinal fluid, and massive inflammatory cells infiltration in the brain. Following on previous research projects and on our aims to evaluate the brain lesions in dogs with VL and to investigate the mechanisms by which it occurs, we propose to evaluate the occurrence of inflammatory mediators within the CNS (brain and cerebrospinal fluid) and in the periphery (spleen, serum and PBMC) of dogs naturally infected by L. chagasi, including the enzymes COX-2, 5-LOX and iNOS, the eicosanoids PGE2 and LTB4, nitric oxide, lipid bodies in leukocytes, the gene expression of the chemokines MCP-1, MCP-2, MIP-1alpha, MIP-1beta, RANTES, CXCL-10 and CX3CL1, the presence of albumin and IgG as well as of the IgG receptors Fc-gammaRI and Fc-gammaRIII. The occurrence of the protozoan within the CNS will also be investigated.

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Scientific publications (4)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
MELO, GUILHERME D.; SILVA, JOSE EDUARDO S.; GRANO, FEMANDA G.; SOUZA, MILENA S.; MACHADO, GISELE F. Leishmania infection and neuroinflammation: Specific chemokine profile and absence of parasites in the brain of naturally-infected dogs. Journal of Neuroimmunology, v. 289, p. 21-29, DEC 15 2015. Web of Science Citations: 6.
MELO, G. D.; GRANO, F. G.; SILVA, J. E. S.; KREMER, B. E.; LIMA, V. M. F.; MACHADO, G. F. Blood-brain barrier disruption during spontaneous canine visceral leishmaniasis. PARASITE IMMUNOLOGY, v. 37, n. 12, p. 635-645, DEC 2015. Web of Science Citations: 4.
MELO, G. D.; SILVA, J. E. S.; GRANO, F. G.; HOMEM, C. G.; MACHADO, G. F. Compartmentalized gene expression of toll-like receptors 2, 4 and 9 in the brain and peripheral lymphoid organs during canine visceral leishmaniasis. PARASITE IMMUNOLOGY, v. 36, n. 12, p. 726-731, DEC 2014. Web of Science Citations: 10.
GRANO, FERNANDA G.; MELO, GUILHERME D.; BELINCHON-LORENZO, SILVIA; GOMEZ-NIETO, LUIS C.; MACHADO, GISELE F. First detection of Leishmania infantum DNA within the brain of naturally infected dogs. Veterinary Parasitology, v. 204, n. 3-4, p. 376-380, AUG 29 2014. Web of Science Citations: 7.
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
MELO, Guilherme Dias de. Leishmaniose visceral e o sistema nervoso central: inflamação nas infecções natural canina e experimental em camundongos. 2015. 125 f. Doctoral Thesis - Universidade Estadual Paulista "Júlio de Mesquita Filho" Faculdade de Medicina Veterinária..

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