New hybrid proteins based on erythropoietin (EPO), EPO-TR and EPO-Fc, and their mutant forms, MEPO-Fc and MEPO-TR, which lack hematopoietic activity but retain the cytoprotective properties of erythropoietin, were created via genetic engineering. The assessment of the antiamnesic efficiency of the obtained proteins was conducted on the 4th day after bilateral photothrombosis of the medial prefrontal cortex of rats and it was dependent on the strength of the conditioned passive avoidance reflex

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... efore ischemia. The concentration of S100b protein, a glial marker of brain tissue damage in the serum of rats, was assessed using enzyme-linked immunosorbent assay (ELISA) within the same period. A one-time intranasal administration of erythropoietin derivatives EPO-Fc and EPO-TR, as well as their mutated forms, MEPO-Fc and MEPO-TR, at a dose of 50 mg/kg, one hour after ischemic brain cortex injury, was associated with the preservation of the skill that was developed before ischemia. A significant decrease in the level of S100b protein in serum was found when EPO-TR was administered. Administration of the other tested derivatives showed a tendency to decrease the S100b level, which was most pronounced in animals treated with MEPO-TR. Our results confirm the neuroprotective efficacy of these novel proteins as potential drugs for the treatment of experimental focal ischemic brain damage.