Abstract

Research on the pathology of spinal cord injury (SCI) has been recently focused on oxidative radical-induced stress and inflammation associated neuronal apoptosis. However, the study of neurorepair and the underlying mechanism in SCI model has been limited. In this study, we investigated the effects of erythropoietin plus nerve growth factor (EPO + NGF) on neurologic and histopathologic changes after SCI and explored its anti-apoptotic role after SCI. Intravenous injection four times a week over a period of 4 weeks of EPO plus NGF (5000 & 2000 U /kg respectively) in male rats following SCI by whole body gamma irradiation caused significant decrease in 8 hydroxyguanosine (8-HDG) and heat shock protein 70 (HSP70). To investigate the possible mechanism, anti-oxidant effect of EPO plus NGF was assessed by measuring superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT) and GSH levels after SCI. EPO plus NGF treatment reversed the decrease of SOD activity and increase of MDA level caused by SCI, suggesting its anti-oxidant role in response to the injury. In addition, EPO plus NGF treatment, after SCI, restored the concentration of neurotransmitters to near normal values seen in control rats after 4 weeks of treatment. Assays for DNA damage in bone marrow cells as well as in spinal cord of rats by chromosomal aberrations, and micronucleus assay and DNA fragmentation techniques were performed in this study. Data showed that the frequency of total chromosomal aberrations and number of micronucleated polychromatic erythrocytes (MNPCE) in animals that received erythropoietin and nerve growth factor after radiation were lower than that in radiated animals that had not been treated with erythropoietin and nerve growth factor. Also, the percentage of DNA fragmentation was reduced after treatment of radiated animals with erythropoietin and nerve growth factor. Further, histopathological alternations were evaluated with H.E. staining that showed a restored SC histology after EPO plus NGF administration.

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