Delayed administration of recombinant human erythropoietin reduces apoptosis and inflammation and promotes myelin repair and functional recovery following spinal cord compressive injury in rats

Article type: Research Article

Authors: Yang, Liuzhu^{a; b; 1} | Yan, Xinping^{a; 1} | Xu, Zunying^a | Tan, Wei^a | Chen, Zhong^{a; *} | Wu, Bo^a

Affiliations: [a] Department of Orthopedics, Southern Medical University, Zhujiang Hospital, Guangzhou, Guangdong, China | [b] Department of Orthopedics, Hezhou city pepole’s hospital, Hezhou, Guangxi, China

Correspondence: [*] Corresponding author: Zhong Chen, MD and PhD, Department of Orthopedics, Southern Medical University, Zhujiang Hospital, 253# industry road, 510280, Guangzhou, Guangdong, China. Tel.: +86 013725198801; Fax: +86 02061643788; E-mail: [email protected].

Note: [1] These authors contributed equally to this work.

Abstract: Purpose: A previous study showed that a 1-h delay in treatment of thoracic spinal cord injury (SCI) with recombinant human erythropoietin (rhEPO) lacked neuroprotective efficacy. The aim of the present study was to reassess delayed administration of different doses of rhEPO on acute spinal cord compressive injury in rats. Methods: The experiment was divided into first and second stages, which SCI rats were observed for 4 and 28 days, respectively. All rats were randomly divided into four groups at both stages: control group, and rhEPO-3,000U (Unit), rhEPO-4,000U and rhEPO-5,000U groups. SCI rats received rhEPO treatment at different time points. The primary indicators were locomotor recovery, histopathology, apoptotic index, inflammatory index, ultrastructural scoring system and volume of areas of demyelination. Results: The most significant locomotor functional and histopathological improvements and the best myelin protection were observed after administration of 5,000 U/kg rhEPO. rhEPO at 3,000, 4,000 and 5,000 U/kg showed similar ultrastructural neuroprotection, as well as similar inhibition of apoptosis and regulation of inflammation. Conclusion: Delayed administration of rhEPO can reduce apoptosis and inflammation, and promote myelin repair and functional recovery following spinal cord compressive injury in rats.

Keywords: Erythropoietin, delayed treatment, spinal cord injury, myelin, functional recovery, rats

DOI: 10.3233/RNN-150498

Journal: Restorative Neurology and Neuroscience, vol. 34, no. 4, pp. 647-663, 2016