Beneficial effect of erythropoietin on experimental allergic encephalomyelitis

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Abstract
We have known for a long time that erythropoietin signaling plays a key role in bone marrow erythrocyte proliferation. However, recent studies have indicated that erythropoietin also may have protective effects on the nervous system. This unexpected role remains incompletely characterized. To investigate the potential neuroprotective role of erythropoietin in the central nervous system, we assessed its effects on a well‐characterized autoimmune demyelinating model of multiple sclerosis–myelin oligodendrocyte glycoprotein‐induced experimental autoimmune encephalomyelitis (EAE) in the mouse. We found that erythropoietin administered intravenously for 14 days after the onset of symptoms reduced both disease severity and duration of maximum impairment at dose levels as low as 50U/kg (p < 0.001). We assessed the neuropathology of diseased spinal cords and found that erythropoietin‐treated EAE animals had reduced axonal damage, inflammatory cell infiltration and demyelination, and diminished blood–brain barrier leakage when compared with saline‐treated EAE controls. Moreover, the pronounced upregulation of spinal cord major histocompatibility complex (MHC) class II expression found in saline‐treated EAE was significantly reduced in erythropoietin‐treated animals, a finding we replicated in vitro, using microglial cultures. The notion that short‐term erythropoietin therapy might be of clinical benefit in human autoimmune demyelinating diseases needs investigation. Ann Neurol 2004; 56: 767‒777