Peripheral inflammatory stimulus exacerbates the ongoing damage in an inflammatory model of demyelination

FERRARI, CC; MURTA, V; PITOSSI, F

Praga

Congreso; Euroglia 2011; 2011

European Meeting on Glial Cells in Health and Disease

Inflammatory events have been described as responsible for both demyelination and as subsequent remyelination. Pro-inflammatory cytokines such as Interleukin 1b (IL-1), Interferon (IFN-g) and tumor necrosis factor (TNF-a) represent noxious molecules to the myelin sheaths and myelinating cells. In particular, the proinflammatory cytokine IL-1 is considered one of the most important mediators in the pathogenesis of inflammatory diseases. The role of inflammation in the progression of neurodegenerative disease remains still obscure. In addition, peripheral inflammation can trigger the synthesis of cytokines in the CNS (Pitossi et al., 1997). Recent studies have revealed that a peripheral pro-inflammatory stimuli can exacerbate ongoing central damage (Perry et al., 2003, Vallieres et al., 2006, Perry et al., 2007, Godoy et al., 2008{Perry, 2004 #320). Peripheral pro-inflammatory stimuli can switch the microglia to an aggressive state inducing a more robust response in the CNS. Clinical and experimental studies of Parkinson`s disease (PD) and Alzheimer have demonstrated that peripheral infections worsen the symptoms of the disease (Penderis et al., 2003, Perry et al., 2007, Pott Godoy et al., 2010, Ferrari and Tarelli, 2011). Our laboratory, has shown that a peripheral pro-inflammatory stimuli exacerbated the neurodegeneration in Parkinson’s Disease (PD) (Godoy et al., 2008, Ferrari and Tarelli, 2011). Only one clinical study has demonstrated that symptoms of EM are exacerbated in a temporal window close to a systemic infection (Buljevac et al., 2002). However, no studies in experimental models have been done until now. We have developed a model that long term expression of IL-1b induced neutrophil infiltration, blood brain barrier breakdown and reversible demyelination (Ferrari et al., 2004). Therefore, we have generated a model of relapsing/remitting MS to study in isolation the innate immune system components. We proposed to study the pathology of peripheral inflammations on the demyelination and remyelination processes in a novel experimental model induced by the chronic expression of IL-1b in the Central Nervous System (CNS).