Erythropoietin and erythropoietin receptor expression after experimental spinal cord injury encourages therapy by exogenous erythropoietin.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Grasso
Giovanni
G
Department of Neurosurgery, University of Messina, Messina, Italy. Giovanni.Grasso@unime.it
Sfacteria
Alessandra
A
Passalacqua
Marcello
M
Morabito
Antonio
A
Buemi
Michele
M
Macrì
Battesimo
B
Brines
Michael L
ML
Tomasello
Francesco
F
D000783:Aneurysm / Q000209:etiology; D000818:Animals; D004195:Disease Models, Animal; D004921:Erythropoietin / Q000502:physiology* / Q000627:therapeutic use*; D005786:Gene Expression Regulation; D008297:Male; D009474:Neurons / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017467:Receptors, Erythropoietin / Q000502:physiology*; D011994:Recombinant Proteins; D013117:Spinal Cord Compression / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000503:physiopathology*
D017467:Receptors, Erythropoietin; D011994:Recombinant Proteins; D004921:Erythropoietin