Preventive effect of erythropoietin on spinal cord cell apoptosis following acute traumatic injury in rats

• Published in: Spine (Philadelphia, Pa. 1976) Vol. 31; no. 21; pp. 2432 - 2438
• Main Authors: ARISHIMA, Yoshiya, SETOGUCHI, Takao, YAMAURA, Ichiro, YONE, Kazunori, KOMIYA, Setsuro
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA Lippincott 01-10-2006; Hagerstown, MD
• Subjects: Animals; Apoptosis - drug effects; Apoptosis - physiology; Biological and medical sciences; Cells, Cultured; Cerebrospinal fluid. Meninges. Spinal cord; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Erythropoietin - pharmacology; Erythropoietin - therapeutic use; Humans; Injuries of the nervous system and the skull. Diseases due to physical agents; Male; Medical sciences; Mice; Mice, Inbred ICR; Nervous system (semeiology, syndromes); Neurology; Neuroprotective Agents - pharmacology; Neuroprotective Agents - therapeutic use; Rats; Rats, Wistar; Recombinant Proteins; Spinal Cord - drug effects; Spinal Cord - pathology; Spinal Cord - physiology; Spinal Cord Injuries - drug therapy; Spinal Cord Injuries - pathology; Spinal Cord Injuries - prevention & control; Traumas. Diseases due to physical agents; spinal cord injury; Spinal cord; Nervous system diseases; Vertebral canal; Erythropoietin; Rat; secondary injury; Rodentia; Central nervous system; Prevention; Vertebrata; Mammalia; Animal; Spinal cord trauma; Central nervous system disease; Spinal cord disease; Apoptosis
• ISSN: 0362-2436; 1528-1159
• DOI: 10.1097/01.brs.0000239124.41410.7a

Using a rat spinal cord injury (SCI) model, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL), anti-active caspase-3 antibody staining, histological examination, and histochemical studies were used to examine the antiapoptotic effect of erythropoietin.
To evaluate in detail the antiapoptotic effect of erythropoietin following SCI.
Although some investigators have reported antiapoptotic effects of erythropoietin using the TUNEL method, it has not been determined whether erythropoietin can prevent both acute neuronal death and secondary injury. Therefore, we examined the temporal and spatial effects of erythropoietin using TUNEL and active caspase-3 following SCI.
An in vitro study used a cerebrocortical culture in which the antiapoptotic effect of erythropoietin was examined after N-methyl-D-aspartate treatment. Using an in vivo study, rats with SCI received erythropoietin intraperitoneally, and were examined histologically and immunohistochemically with TUNEL, active caspase-3, and cell markers between 6 hours and 7 days after injury.
Cerebrocortical culture confirmed an antiapoptotic effect of erythropoietin. Erythropoietin treatment significantly decreased TUNEL-positive apoptotic neurons and oligodendrocytes as early as 6 hours after SCI in rats. This antiapoptotic effect was observed until 7 days after injury. In addition, erythropoietin treatment significantly decreased the number of active caspase-3 immunoreactive cells within the SCI. In the in vitro study, cerebrocortical culture confirmed an antiapoptotic effect of erythropoietin.
These findings suggest that exogenous erythropoietin decreases the number of apoptotic cells observed between the very early and subchronic stages following traumatic SCI.