title: Differential alterations in the activity of matrix metalloproteinases within the nervous tissue of dogs in distinct manifestations of visceral leishmaniasis.
abstract: Canine visceral leishmaniasis is an important emerging disease with a multitude of clinical symptoms, including neurological alterations. Matrix metalloproteinases (MMP) are proteases implicated with the extracellular matrix remodelling and, within the central nervous system, these enzymes are involved with blood-brain-barrier disruption and inflammation. To establish the involvement of MMP-2 and -9 within the nervous tissue of dogs with spontaneous visceral leishmaniasis, fragments of nervous tissue from oligosymptomatic (n=9), symptomatic (n=8), neurological (n=12) and normal dogs (n=8) were subjected to zymographic and to immunohistochemical analysis. Immunohistochemistry evidenced MMP-2 staining in inflammatory cells inside and outside blood vessels. MMP-9 was found in endothelial cells and in the ependyma. Zymographic evaluation revealed only the latent forms of MMP-2 and -9 within the nervous tissue. ProMMP-9 activity in the infected animals was found higher than the normal dogs, but with no difference among the infected dogs. Oligosymptomatic dogs presented the highest proMMP-2 activity, followed by the symptomatic and then, by the neurological and the normal dogs. In summary, the nervous tissue compartment seems to be preserved in dogs with VL, due to the absence of active MMPs, even though the elevated levels of proMMP-2 and -9 would indicate a pro-inflammatory state in the brain.
authors.affiliation: Departamento de Clínica, Cirurgia e Reproducão Animal, Universidade Estadual Paulista "Júlio de Mesquita Filho" (UNESP), School of Veterinary Medicine, FO-Araçatuba, São Paulo, Brazil. giselem@fmva.unesp.br
authors.forename: Gisele F
authors.initials: GF
authors.lastname: Machado
authors.forename: Guilherme D
authors.initials: GD
authors.lastname: Melo
authors.forename: Olívia C
authors.initials: OC
authors.lastname: Moraes
authors.forename: Milena S
authors.initials: MS
authors.lastname: Souza
authors.forename: Mary
authors.initials: M
authors.lastname: Marcondes
authors.forename: Sílvia H V
authors.initials: SH
authors.lastname: Perri
authors.forename: Rosemeri O
authors.initials: RO
authors.lastname: Vasconcelos
mesh_terms: D000818:Animals; D002493:Central Nervous System Diseases / Q000201:enzymology / Q000276:immunology / Q000469:parasitology / Q000662:veterinary*; D004283:Dog Diseases / Q000201:enzymology / Q000276:immunology / Q000469:parasitology*; D004285:Dogs; D004591:Electrophoresis, Polyacrylamide Gel / Q000662:veterinary; D005260:Female; D007150:Immunohistochemistry / Q000662:veterinary; D007893:Leishmania donovani / Q000276:immunology*; D007898:Leishmaniasis, Visceral / Q000201:enzymology / Q000276:immunology / Q000469:parasitology / Q000821:virology*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000276:immunology*; D020780:Matrix Metalloproteinase 9 / Q000276:immunology*; D018709:Statistics, Nonparametric
chemical_list: D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9