| Texto completo | |
| Autor(es): |
Bombeiro, Andre Luis
[1, 2]
;
D'Imperio Lima, Maria Regina
[1]
;
Chadi, Gerson
[2]
;
Alvarez, Jose Maria
[1]
Número total de Autores: 4
|
| Afiliação do(s) autor(es): | [1] Univ Sao Paulo, Dept Immunol, Inst Biomed Sci, BR-05508000 Sao Paulo - Brazil
[2] Univ Sao Paulo, Sch Med, Dept Neurol, Neurogenerat Ctr, BR-05508000 Sao Paulo - Brazil
Número total de Afiliações: 2
|
| Tipo de documento: | Artigo Científico |
| Fonte: | NEUROIMMUNOMODULATION; v. 17, n. 2, p. 67-78, 2010. |
| Citações Web of Science: | 8 |
| Resumo | |
Background/Aim: Chagas' disease is caused by Trypanosoma cruzi and occurs in most Latin American countries. The protozoan may colonize the central nervous system (CNS) of immune-compromised human hosts, thus causing neuronal disorders. Systemic control of the intracellular forms of the parasite greatly depends on the establishment of a TH1 response and subsequent nitric oxide (NO) release. At the CNS, it is known that low concentrations of NO promote neuronal survival and growth, while high concentrations exert toxic effects and neuron death. Accounting for NO production by astrocytes is the glia-derived factor S100 beta, which is overproduced in some neurodegenerative diseases. In the current work, we studied the expression of NO, interferon (IFN)-gamma and S100 beta in the spinal cord tissue of IL-12p40KO mice infected with T. cruzi, a model of neurodegenerative process. Methods: IL-12p40KO and wild-type (WT) female mice infected with T. cruzi Sylvio X10/4 (10(5) trypomastigotes, intraperitoneally) were euthanized when IL-12p40KO individuals presented limb paralysis. Spinal cord sections were submitted to immunohistochemical procedures for localization of neurofilament, laminin, nitrotyrosine, NO synthases (NOS), IFN-gamma and S100 beta. The total number of neurons was estimated by stereological analysis and the area and intensity of immunoreactivities were assessed by microdensitometric/morphometric image analysis. Results: No lesion was found in the spinal cord sections of WT mice, while morphological disarrangements, many inflammatory foci, enlarged vessels, amastigote nests and dying neurons were seen at various levels of IL-12p40KO spinal cord. Compared to WT mice, IL-12p40KO mice presented a decrement on total number of neurons (46.4%, p<0.05) and showed increased values of immunoreactive area for nitrotyrosine (239%, p<0.01) and NOS (544%, p<0.001). Moreover, the intensity of nitrotyrosine (16%, p<0.01), NOS (38%, p<0.05) and S100 beta (21%, p<0.001) immunoreactivities were also augmented. No IFN-gamma labeled cells were seen in WT spinal cord tissue, contrary to IL-12p40KO tissue that displayed inflammatory infiltrating cells and also some parenchymal cells positively labeled.Conclusion: We suggest that overproduction of NO may account for neuronal death at the spinal cord of T. cruzi-infected IL-12p40KO mice and that IFN-gamma and S100 beta may contribute to NOS activation in the absence of IL-12. Copyright (C) 2009 S. Karger AG, Basel (AU) | |
| Processo FAPESP: | 06/50054-6 - A interacao trypanosoma cruzi - hospedeiro no modelo murino de doenca de chagas: analise dos elementos envolvidos no controle do parasita e no desenvolvimento da patologia. |
| Beneficiário: | José Maria Álvarez Mosig |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |
| Processo FAPESP: | 06/53116-2 - Estudos neuroimunológicos da Doença de Chagas experimental: análises histomoleculares da medula espinal de camundongos imunocompetentes e deficientes em IL-12 e IL-23 infectados com Trypanossoma cruzi da cepa Sylvio X10/4 |
| Beneficiário: | André Luis Bombeiro |
| Modalidade de apoio: | Bolsas no Brasil - Doutorado Direto |
| Processo FAPESP: | 07/00491-3 - Análise do potencial das células de Schwann cultivadas e tratadas com o PEDF favorecem o trofismo de neurônios medulares in vitro a induzirem a regeneração e a recuperação motora de ratos submetidos ao trauma contuso da medula espinal pelo Impactor |
| Beneficiário: | Gerson Chadi |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |