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Erythropoietin (EPO) has neuroprotective effects in many models of damage and disease of the nervous system where neuroinflammationplays a substantial role, including experimental autoimmune encephalomyelitis (EAE), the animal model of multiple sclerosis(MS). Since the first pioneering studies, in which EPO was shown to protect rats with acute EAE mainly by inhibiting inflammation,many other studies have pointed out other mechanisms of protection, including oligodendrogenesis and inhibition of axonaldamage.
Here we review the preclinical studies in which EPO has shown therapeutic efficacy in several models of EAE in mice and rats. Moreover, we report in detail the protocol to administer EPO to mice with myelin oligodendrocyte glycoprotein (MOG)-inducedchronic progressive EAE, and a representative result. In this model, EPO inihibits the clinical score of the disease whenadministered according to a preventive but also to a therapeutic schedule, and therefore at disease onset, suggesting thatit might not only inhibit inflammation but also actively stimulate repair.