Erythropoietin and Erythropoietin Receptor Expression after Experimental Spinal Cord Injury Encourages Therapy by Exogenous Erythropoietin

Abstract

Erythropoietin (EPO) is a pleiotropic cytokine originally identified for its role in erythropoiesis. Recent studies have demonstrated that EPO and its receptor (EPO-R) are expressed in the central nervous system, where EPO exerts neuroprotective functions. Because the expression of the EPO and EPO-R network is poorly investigated in the central nervous system, the aim of the present study was to investigate whether the resident EPO and EPO-R network is activated in the injured nervous system. A well-standardized model of compressive spinal cord injury in rats was used. EPO and EPO-R expression was determined by immunohistochemical analysis at 8 hours and at 2, 8, and 14 days in the spinal cord of injured and noninjured rats. In noninjured spinal cord, weak immunohistochemical expression of EPO and EPO-R was observed in neuronal and glial cells as well as in endothelial and ependymal cells. In injured rats, a marked increase of expression of EPO and EPO-R was observed in neurons, vascular endothelium, and glial cells at 8 hours after injury, peaking at 8 days, after which it gradually decreased. Two weeks after injury, EPO immunoreactivity was scarcely detected in neurons, whereas glial cells and vascular endothelium expressed strong EPO-R immunoreactivity. These observations suggest that the local EPO and EPO-R system is markedly engaged in the early stages after nervous tissue injury. The reduction in EPO immunoexpression and the increase in EPO-R staining strongly support the possible usefulness of a therapeutic approach based on exogenous EPO administration.