Effects of Erythropoietin in Hypoxia-Induced Ischemia on Differentiated Human Neuroblastoma SH-SY5Y and Rat Stroke Model / 대한정신약물학회지

ABSTRACT

OBJECTIVE: The hematopoietic cytokine, erythropoietin (EPO) is known to have neuroprotective effects including promotion of neuronal survival and regeneration after ischemic injury. This study was to investigate the effects of EPO on synaptogenesis and neural restoration in the ischemic condition on neuronal differentiated SH-SY5Y cells and on the behaviors in rat animal model induced by middle cerebral artery occlusion. METHODS: We analyzed the neurite outgrowth and the gene expression of differentiated human neuroblastoma SH-SY5Y cells after the hypoxic stress. Moreover, we performed the motor functional behavior test in EPO treatment of Sprague Dawley rats following cerebral ischemia induced by middle cerebral artery's occlusion (MCAO). RESULTS: Treatment of 2 and 10 units EPO for 1 week showed increase of neurite outgrowth SH-SY5Y cells, compared with non-treatment group (p < 0.05). The results of reverse transcriptase-polymerose chain reaction (RT-PCR) also showed that both synaptophysin (SYP) genes and Growth Associated protein 43 (GAP43) genes in EPO treated cells were significant increased compared with non-treated ischemic group, respectively. The foot fault behavior was recovered in MCAO with EPO treatment group than MCAO group, significantly. CONCLUSION: The elongation of neurite and the increased expressions of SYP and GAP43, and recovered behavioral evidence in the EPO treatment are involved in possible role in neural restoration and synaptogenesis in hypoxic injuried brain. In this study, we suggest that EPO treatment will be may supportive medication to stroke patients to improve the functional brain disturbance.