Erythropoietin prevents motor neuron apoptosis and neurologic disability in experimental spinal cord ischemic injury.
The cytokine erythropoietin (EPO) possesses potent neuroprotective activity against a variety of potential brain injuries, including transient ischemia and reperfusion. It is currently unknown whether EPO will also ameliorate spinal cord injury. Immunocytochemistry performed using human spinal cord sections showed abundant EPO receptor immunoreactivity of capillaries, especially in white matter, and motor neurons within the ventral horn. We used a transient global spinal ischemia model in rabbits to test whether exogenous EPO can cross the blood-spinal cord barrier and protect these motor neurons. Spinal cord ischemia was produced in rabbits by occlusion of the abdominal aorta for 20 min, followed by saline or recombinant human (rHu)-EPO (350, 800, or 1,000 units/kg of body weight) administered intravenously immediately after the onset of reperfusion. The functional neurological status of animals was better for rHu-EPO-treated animals 1 h after recovery from anesthesia, and improved dramatically over the next 48 h. In contrast, saline-treated animals exhibited a poorer neurological score at 1 h and did not significantly improve. Histopathological examination of the affected spinal cord revealed widespread motor neuron injury associated with positive terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling in control but not in rHu-EPO-treated animals. These observations suggest both an acute as well as a delayed beneficial action of rHu-EPO in ischemic spinal cord injury. Because rHu-EPO is currently used widely with an excellent safety profile, clinical trials evaluating its potential to prevent motor neuron apoptosis and the neurological deficits that occur as a consequence of ischemic injury are warranted.
Celik
Murat
M
Department of Anesthesiology, Dokuz Eylül University School of Medicine, Izmir 35340, Turkey.
Gökmen
Necati
N
Erbayraktar
Serhat
S
Akhisaroglu
Mustafa
M
Konakc
Selman
S
Ulukus
Cagnur
C
Genc
Sermin
S
Genc
Kursad
K
Sagiroglu
Emel
E
Cerami
Anthony
A
Brines
Michael
M
D000818:Animals; D017209:Apoptosis; D004305:Dose-Response Relationship, Drug; D004921:Erythropoietin / Q000494:pharmacology* / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007511:Ischemia; D008297:Male; D009046:Motor Neurons / Q000473:pathology*; D011817:Rabbits; D011994:Recombinant Proteins / Q000378:metabolism; D013116:Spinal Cord / Q000473:pathology*; D013119:Spinal Cord Injuries / Q000378:metabolism*; D013997:Time Factors
D011994:Recombinant Proteins; D004921:Erythropoietin