Protective effects of erythropoietin in traumatic spinal cord injury by inducing the Nrf2 signaling pathway activation

BACKGROUND: Erythropoietin has demonstrated neuroprotective effects against traumatic spinal cord injury (SCI), but the underlying mechanisms remain unclear. The signaling pathway of an antioxidant transcription factor, nuclear factor erythroid 2-related factor 2 (Nrf2), has been shown to play an important role in protecting SCI-induced secondary spinal cord damage. This study was undertaken to explore the effect of recombinant human erythropoietin (rhEPO) on the activation of Nrf2 signaling pathway and secondary spinal cord damage in rats after SCI. METHODS: Adultmale Sprague-Dawley rats were subjected to laminectomy at T8-T9 and compression with avascular clip. Three groups were analyzed: (1) sham group, (2) SCI group, and (3) SCI + rhEPO group (n = 16 per group). In the SCI + rhEPO group, rhEPO was administered at a dose of 5,000 IU/kg at 30 minutes after SCI. Spinal cord samples were extracted at 72 hours after the trauma. RESULTS: As a result, we found that the treatment with rhEPO markedly up-regulated the messenger RNA expressions and activities of Nrf2 signaling pathway-related agents, including Nrf2, NAD(P) H: quinone oxidoreductase 1(NQO1), and glutathione S-transferase. The administration of rhEPO also significantly ameliorated the secondary spinal cord damage, as shown by a decreased severity of locomotion deficit, spinal cord edema, and apoptosis. CONCLUSION: Post-SCI rhEPO administration induces Nrf2-mediated cytoprotective response in the injured spinal cord, and this may be a mechanism whereby rhEPO improves the outcome following SCI. (J Trauma Acute Care Surg. 2014; 76: 1228-1234. Copyright (C) 2014 by Lippincott Williams & Wilkins)