Peripheral inflammatory stimulus exacerbates the ongoing central damage in neurodegenerative diseases

CARINA FERRARI

Montevideo

Simposio; Symposium Neuron-Glia interactions in health and disease: from Basic Biology to translational neuroscience; 2012

Institut Pasteur de Montevideo

Multiple sclerosis is a chronic inflammatory disease characterized by demyelination and remyelination events. Etiology of the disease is still not clear and therapeutic interventions fail in reducing disability or influencing the disease progression. Pro-inflammatory cytokine Interleukin-1beta (IL-1) is associated with a spectrum of neuroinflammatory processes in neurodegenerative diseases. We previously studied that the chronic expression of IL1 in the striatum, induced neutrophil infiltration, micro and astroglial activation and reversible demyelination and that the response to a secondary stimulus depends on whether the primary lesion is still active or not . The aim of this talk is to describe our results on repeated central injections of a pro-inflammatory stimulus and to analyze the effect of a peripheral inflammation on an ongoing inflammatory damage in the striatum. We used and adenovector expressing IL-1 (AdIL-1) to induce chronic expression in the striatum. Animals previously injected in the striatum with the AdIL-1, were injected endovenously with a pro-inflammatory stimuli 30 days after central stimulus. Animals injected with AdIL-1/AdIL-1 exhibited an exacerbation of both inflammatory and demyelinating response compared to AdIL-1/Adbgal. Animals AdIL-1/Adbgal exhibited a similar response to that observed in non-peripherally injected animals. Astroglia and microglia response were in accordance with the inflammatory response. In summary, pro-inflammatory stimuli exacerbate both inflammatory and demyelinating events. This response is accompanied by microglia and astroglia activation, and therefore increases the ongoing nervous tissue damage. Our data model provides data evidenced by the chronic expression of a unique proinflammatory cytokine, which allowed us to dissect the effect of this cytokine or its downstream components as major mediators of demyelination in chronic inflammatory and demyelinating diseases and analyse the effect of peripheral inflammation on central damage.