Elsevier

Neuroscience Letters

Volume 490, Issue 1, 18 February 2011, Pages 57-62
Neuroscience Letters

Recombinant human erythropoietin prevents motor neuron apoptosis in a rat model of cervical sub-acute spinal cord compression

https://doi.org/10.1016/j.neulet.2010.12.025Get rights and content

Abstract

The objective of the study was to investigate the effects of recombinant human erythropoietin (rhEPO) in a rat model of cervical sub-acute spinal cord compression. 80 Wistar rats were randomly divided into 4 groups. Rats in the sham group (Group A, n = 5) underwent surgical procedures without cervical spinal cord compression; while rats in other groups were subjected to the spinal compression process. In the control group (Group B, n = 25), rats received an i.v. injection of 1 mL saline at day 7 post-surgery. Rats in the low-dose group (Group C, n = 25) and the high-dose group (Group D, n = 25) were treated with rhEPO at 500 units/kg body-weight and 5000 units/kg, respectively, via intravenous injection at day 7 post surgery. Limb motor function was scored by Basso–Beattie–Bresnahan (BBB) standards at 3, 7, 14, 21 and 28 days post-surgery. The distribution and quantities of EPO and its receptor (EPO-R) in the compressed segment of the spinal cord were detected by immunohistochemistry. Motor neuron apoptosis in the spinal cord was evaluated using TUNEL staining and flow cytometry at the indicated time points. Finally, IL-8, TNF-α, IL-6, and IL-1β levels in the compressed cervical spinal cord were determined by ELISA within the lesion epicenter at each time point post-surgery. The data suggest that expression of EPO-R was significantly increased following sub-acute cervical spinal cord compression; Groups C and D exhibited better BBB scores at all observed time points compared with the control group (p < 0.01). Using TUNEL staining and FCM, we observed that rhEPO profoundly inhibited motor neuron apoptosis in the spinal cord at day 21 (p < 0.01). Additionally, treatment with rhEPO halted the elevation of inflammatory cytokines. rhEPO administration decreased motor neuron apoptosis in the cervical spinal cord, improved motor functions and reduced the inflammatory response in a sub-acute cervical spinal cord compression model. Moreover, sustained treatment with low doses of rhEPO revealed a positive therapeutic effect.

Research highlights

▶ Established an experimental CSSCC model in rats. ▶ The rhEPO effection in the 28 day period. ▶ Given rhEPO at 7 days after surgery. ▶ One time low/high dose of rhEPO treatment.

Section snippets

Acknowledgements

The authors wish to thank Dr. Han Kun for his expertise and technical assistance, Prof. Xiuli Ju and Dr. Yingqian Zhang for their kind review of the manuscript, and Dr. Li Ming and Dr. Xia Qigan for their outstanding animal husbandry. This work was supported by grant from the National Natural Science Foundation of China (No. 30271318 M.H.).

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