CNS response to a second pro-inflammatory event depends on whether the primary demyelinating lesion is active or resolved.
Brain Behav Immun
; 26(7): 1102-15, 2012 Oct.
Article
em En
| MEDLINE
| ID: mdl-22824737
ABSTRACT
Interleukin-1ß (IL-1ß) is considered to be one of the most important mediators in the pathogenesis of inflammatory diseases, particularly in neurodegenerative diseases such as multiple sclerosis (MS). MS is a chronic inflammatory disease characterized by demyelination and remyelination events, with unpredictable relapsing and remitting episodes that seldom worsen MS lesions. We proposed to study the effect of a unique component of the inflammatory process, IL-1ß, and evaluate its effect in repeated episodes, similar to the relapsing-remitting MS pathology. Using adenoviral vectors, we developed a model of focal demyelination/remyelination triggered by the chronic expression of IL-1ß. The long-term expression of IL-1ß in the striatum produced blood-brain barrier (BBB) breakdown, demyelination, microglial/macrophage activation, and neutrophil infiltration but no overt neuronal degeneration. This demyelinating process was followed by complete remyelination of the area. This simple model allows us to study demyelination and remyelination independently of the autoimmune and adaptive immune components. Re-exposure to this cytokine when the first inflammatory response was still unresolved generated a lesion with decreased neuroinflammation, demyelination, axonal injury and glial response. However, a second long-term expression of IL-1ß when the first lesion was resolved could not be differentiated from the first event. In this study, we demonstrated that the response to a second inflammatory stimulus varies depending on whether the initial lesion is still active or has been resolved. Considering that anti-inflammatory treatments have shown little improvement in MS patients, studies about the behavior of specific components of the inflammatory process should be taken into account to develop new therapeutic tools.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Sistema Nervoso Central
/
Doenças Desmielinizantes
/
Inflamação
Limite:
Animals
Idioma:
En
Revista:
Brain Behav Immun
Ano de publicação:
2012
Tipo de documento:
Article