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Neurotoxicology ; 33(3): 347-60, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22330755

RESUMO

Evidence supports the role of inflammation in the development of neurodegenerative diseases. In this work, we are interested in inflammation as a risk factor by itself and not only as a factor contributing to neurodegeneration. We tested the influence of a mild to moderate peripheral inflammation (injection of carrageenan into the paws of rats) on the degeneration of dopaminergic neurons in an animal model based on the intranigral injection of lipopolysaccharide (LPS), a potent inflammatory agent. Overall, the treatment with carrageenan increased the effect of the intranigral injection of LPS on the loss of dopaminergic neurons in the SN along with all the other parameters studied, including: serum levels of the inflammatory markers TNF-α, IL-1ß, IL-6 and C-reactive protein; activation of microglia, expression of proinflammatory cytokines, the adhesion molecule ICAM and the enzyme iNOS, loss of astrocytes and damage to the blood brain barrier (BBB). The possible implication of BBB rupture in the increased loss of dopaminergic neurons has been studied using another Parkinson's disease animal model based on the intraperitoneal injection of rotenone. In this experiment, loss of dopaminergic neurons was also strengthened by carrageenan, without affecting the BBB. In conclusion, our data show that a mild to moderate peripheral inflammation can exacerbate the degeneration of dopaminergic neurons caused by a harmful stimulus.


Assuntos
Gânglios da Base/metabolismo , Dopamina/metabolismo , Neurônios Dopaminérgicos/metabolismo , Encefalite/complicações , Inflamação/complicações , Degeneração Estriatonigral/etiologia , Substância Negra/metabolismo , Animais , Astrócitos/metabolismo , Astrócitos/patologia , Gânglios da Base/patologia , Barreira Hematoencefálica/metabolismo , Barreira Hematoencefálica/patologia , Proteína C-Reativa/metabolismo , Carragenina , Modelos Animais de Doenças , Neurônios Dopaminérgicos/patologia , Encefalite/induzido quimicamente , Encefalite/metabolismo , Encefalite/patologia , Inflamação/induzido quimicamente , Inflamação/metabolismo , Inflamação/patologia , Mediadores da Inflamação/sangue , Molécula 1 de Adesão Intercelular/metabolismo , Interleucina-1beta/sangue , Interleucina-6/sangue , Lipopolissacarídeos , Masculino , Óxido Nítrico Sintase Tipo II/metabolismo , Ratos , Ratos Wistar , Rotenona , Degeneração Estriatonigral/metabolismo , Degeneração Estriatonigral/patologia , Substância Negra/patologia , Fatores de Tempo , Fator de Necrose Tumoral alfa/sangue
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