Neuroprotection of erythropoietin and methylprednisolone against spinal cord ischemia-reperfusion injury

Abstract

Recent research based on various animal models has shown the neuroprotective effects of erythropoietin (EPO). However, few studies have examined such effects of EPO in the clinic. In this study we enrolled patients with spinal cord ischemia-reperfusion (I-R) injury to investigate the clinical application of EPO and methylprednisolone (MP) for the neuroprotection against spinal cord I-R injury. Retrospective analysis of 63 cases of spinal cord I-R injury was performed. The Frankel neurological performance scale was used to evaluate the neurological function after spinal cord injury (SCI), including 12 cases of scale B, 30 cases of scale C, and 21 cases of scale D. These cases were divided into 2 groups: group A (27 cases) got treatment with both EPO and MP; group B (36 cases) got treatment with MP only. The neurological function of patients after treatment was evaluated by American Spinal Cord Injury Association (ASIA) index score, and activity of daily living (ADL) of the patients was also recorded. All patients got follow-up and the follow-up period ranged from 24 to 39 months (mean 26 months). There was no significance difference in neurological function between groups A and B before the treatment (P>0.05). However, the neurological function and ADL scores were significantly improved 1 week, 1 year or 2 years after the treatment compared to those before the treatment (P<0.05), and the improvement was more significant in group A than in group B (P<0.05). It is suggested that the clinical application of EPO and MP provides the neuroprotection against spinal cord I-R injury.

Keywords

erythropoietin / methylprednisolone / neuroprotection / spinal cord / ischemia-reperfusion injury

References

[1] DameC., JuulS., ChristensenR.D.. The biology of erythropoietin in the central nervous system and its neurotrophic and neuroprotective potential. Biol Neonate, 2001, 79(3–4): 228-235

[2] LiuR., SuzukiA., GuoZ., et al.. Intrinsic and extrinsic ery thropoietin enhances neuroprotection against ischemia and reperfusion injury in vitro. J Neurochem, 2006, 96(4): 1101-1110

[3] CapaulM., ZollingerH., SatzN., et al.. Analyses of 94 consecutive spinal cord injury patients using ASIA definition and modified Frankel score classification. Paraplegia, 1994, 32(9): 583-587

[4] EI MasryW.S., TsuboM., KatohS., et al.. Validation of the American Spinal Injury Association (ASIA) motor score and the National Acute Spinal Cord Injury Study (NASCIS) motor score. Spine, 1996, 21(5): 614-619

[5] GrassoG., SfacteriaA., MeliF., et al.. The role of erythropoietin in neuroprotection: therapeutic perspectives. Drug News Perspect, 2007, 20(5): 315-320

[6] OkutanO., SolarogluI., BeskonakliE., et al.. Recombinant human erythropoietin decreases myeloperoxidase and caspase-3 activity and improves early functional results after spinal cord injury in rats. J Clin Neurosci, 2007, 14(4): 364-368

[7] ChoiB.H., HaY., AhnC.H., et al.. A hypoxia-inducible gene expression system using erythropoietin 3′ untranslated region for the gene therapy of rat spinal cord injury. Neurosci Lett, 2007, 412(2): 118-122

[8] Vitellaro-ZuccarelloL., MazzettiS., MadaschiL., et al.. Erythropoietin-mediated preservation of the white matter in rat spinal cord injury. Neuroscience, 2007, 144(3): 865-877

[9] MannC., LeeJ.H., LiuJ., et al.. Delayed treatment of spinal cord injury with erythropoietin or darbepoetin—a lack of neuroprotective efficacy in a contusion model of cord injury. Exp Neurol, 2008, 211(1): 34-40

[10] Vitellaro-ZuccarelloL., MazzettiS., MadaschiL., et al.. Chronic erythropoietin-mediated effects on the expression of astrocyte markers in a rat model of contusive spinal cord injury. Neuroscience, 2008, 151(2): 452-466

[11] FangX.Q., FangM., FanS.W., et al.. Protection of erythropoietin on experimental spinal cord injury by reducing the expression of thrombospondin-1 and transforming growth factor-beta. Chin Med J (Engl), 2009, 122(14): 1631-1635

[12] MatisG.K., BirbilisT.A.. Erythropoietin in spinal cord injury. Eur Spine J, 2009, 18(3): 314-323

[13] KontogeorgakosV.A., VoulgarisS., KorompiliasA.V., et al.. The efficacy of erythropoietin on acute spinal cord injury. An experimental study on a rat model. Arch Orthop Trauma Surg, 2009, 129(2): 189-194

[14] GorioA., MadaschiL., Di StefanoB., et al.. Methylprednisolone neutralizes the beneficial effects of erythropoietin in experimental spinal cord injury. Proc Natl Acad Sci USA, 2005, 102(45): 16 379-16 384

[15] KimM.S., SeoY.K., ParkH.J., et al.. The neuroprotective effect of recombinant human erythropoietin via an antiapoptotic mechanism on hypoxic-ischemic brain injury in neonatal rats. Korean J Pediatr, 2010, 53(10): 898-908

[16] MaieseK., ChongZ.Z., HouJ., et al.. New strategies for Alzheimer’s disease and cognitive impairment. Oxid Med Cell Longev, 2009, 2(5): 279-289

[17] XiongM., ChenS., ZengY., et al.. The effect of erythropoietin on the mobility of bone marrow mesenchymal stem cell to the sites of injured spinal cord. Chin J Exp Surg (Chinese), 2011, 28(4): 618-520