Erythropoietin attenuates neuronal injury and potentiates the expression of pCREB in anterior horn after transient spinal cord ischemia in rats.
BACKGROUND
Recent studies have suggested that EPO activates the CREB transcription pathway and increases BDNF expression and production, which contributes to EPO-mediated neuroprotection. We investigated whether EPO has a neuroprotective effect against ISCI in rats and examined the involvement of CREB protein phosphorylation in this process.


METHODS
Spinal cord ischemia was produced by balloon occlusion of the abdominal aorta below the branching point of the left subclavian artery for 5 minutes, and rHu-EPO (1000 U/kg BW) was administered intravenously after the onset of the reperfusion. Neurologic status was assessed at 1, 24, and, 48 hours. After the end of 48 hours, spinal cords were harvested for histopathologic analysis and immunohistochemistry for pCREB.


RESULTS
All sham-operated rats had a normal neurologic outcome, whereas all ischemic rats suffered severe neurologic deficits after ISCI. Erythropoietin treatment was found to accelerate recovery of motor deficits and prevent the loss of motoneurons in the spinal cord after transient ischemia. Ischemic spinal cord injury induced the phosphorylation of pCREB at the anterior horn of the spinal cord, and EPO treatment significantly potentiated expression of pCREB increase at the anterior horn of the spinal cord.


CONCLUSIONS
These results demonstrate that a single dose of EPO given before ISCI provides significant neuroprotection and potentiates the expression of pCREB in this region.
Sönmez
Ataç
A
Learning Resources Center Research Laboratory, School of Medicine, Dokuz Eylul University Inciralti, TR-35340, Izmir, Turkey. atac.sonmez@deu.edu.tr
Kabakçi
Birol
B
Vardar
Enver
E
Gürel
Duygu
D
Sönmez
Ulker
U
Orhan
Yahya T
YT
Açikel
Unal
U
Gökmen
Necati
N
D000818:Animals; D000870:Anterior Horn Cells / Q000378:metabolism / Q000473:pathology; D050882:CREB-Binding Protein / Q000378:metabolism*; D000068817:Epoetin Alfa; D004921:Erythropoietin / Q000627:therapeutic use*; D006397:Hematinics / Q000627:therapeutic use*; D008297:Male; D009043:Motor Activity / Q000502:physiology; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins; D020127:Recovery of Function / Q000502:physiology; D020760:Spinal Cord Ischemia / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*
D006397:Hematinics; D011994:Recombinant Proteins; D004921:Erythropoietin; D000068817:Epoetin Alfa; D050882:CREB-Binding Protein; C494365:Crebbp protein, rat