Expression of Erythropoietin in the Spinal Cord of Lewis Rats with Experimental Autoimmune Encephalomyelitis

ABSTRACT

BACKGROUND AND PURPOSE: Erythropoietin (Epo), originally recognized for its central role in erythropoiesis, has been shown to improve the outcomes in patients with various neurological disorders. The aim of this study was to elucidate the Epo expression pattern in the spinal cords of Lewis rats with experimental autoimmune encephalomyelitis (EAE) and to assess the systemic effect of Epo during the course of EAE. METHODS: We used an EAE model induced in Lewis rats by immunization with myelin basic protein. Immunized rats were given recombinant human Epo (rhEpo) intraperitoneally at a dose of 5,000 U/kg for 7 consecutive days, either starting on day 3 post-immunization (five rats) or on the day of clinical symptom onset (score > or =1, five rats). After immunization, the rats were observed daily for clinical signs of EAE. Epo expression was investigated by Western blot analysis and immunohistochemistry. RESULTS: Western blot analysis showed that, Epo expression was significantly elevated relative to control in the rat spinal cord during the peak stage of EAE (p<0.05), and then decreased thereafter. Immunohistochemistry demonstrated that Epo was expressed in some neurons and glial cells. Epo immunoreactivity was detected in ED1-positive macrophages and astrocytes in EAE lesions. Furthermore, we found that the intraperitoneal administration of rhEpo reduced both the disease severity and duration of paralysis in EAE rats, and reduced macrophage activity and increased Epo activity. CONCLUSIONS: Based on these findings, we postulate that Epo expression begins to increase at the start of EAE and that rhEpo administration leads to functional recovery from EAE paralysis.