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Inhibition of S100B prevents ex vivo demyelination and improves EAE clinical score

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The autoimmune disease multiple sclerosis (MS), with strong inflammation and neurodegeneration, affects motor and cognitive functions. S100B is increased in CSF, serum and post-mortem plaques of MS patients being correlated… Click to show full abstract

The autoimmune disease multiple sclerosis (MS), with strong inflammation and neurodegeneration, affects motor and cognitive functions. S100B is increased in CSF, serum and post-mortem plaques of MS patients being correlated with demyelination and glial reactivity. We also showed that S100B neutralization has a beneficial outcome in an ex vivo demyelinating model. Here, we first addressed how targeting S100B with pentamidine could prevent MS-related pathogenesis in the ex vivo model. Pentamidine prevented not only demyelination and axonal impairment, but also the exacerbated production of inflammatory factors (TNF-α, IL-1β, HMGB1). Next, we used the in-vivo animal model of MS, the Experimental Autoimmune Encephalomyelitis (EAE), to evaluate if pentamidine could prevent/ameliorate MS disease course. EAE-induced animals when treated with pentamidine reach a lower disease clinical score and have a fast recovery. Our results indicate that S100B is involved in MS pathology and that its inhibition may be a new potential therapy to reduce damage and improve recovery.

Keywords: demyelination; inhibition s100b; clinical score

Journal Title: Free Radical Biology and Medicine
Year Published: 2018

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