RESUMEN
Mutant EPO molecules, deprived of erythropoietic activity, but possessing cytoprotective action, were created by the method of genetic engineering. The assessment of the therapeutic effectiveness of the received mutant proteins was carried out by the retention of the conditioned reflex of passive avoidance (PA), developed before the ischemic injury of rat brain prefrontal cortex, and by the MRI-analysis of ischemic damage volume. Antiamnestic and neuroprotective action of mutant molecules - MERO-Fc and MEPO-TR is investigated on model of photothrombosis of rat brain prefrontal cortex at single intranasal introduction in 1 h after cortex ischemic damage. The neuroprotective (MRI) and antiamnestic (PA) effects of mutant molecules of erythropoietin derivatives are shown.
Asunto(s)
Eritropoyetina , Trombosis Intracraneal , Mutación , Fármacos Neuroprotectores/farmacología , Corteza Prefrontal , Animales , Modelos Animales de Enfermedad , Eritropoyetina/genética , Eritropoyetina/farmacología , Trombosis Intracraneal/inducido químicamente , Trombosis Intracraneal/tratamiento farmacológico , Trombosis Intracraneal/fisiopatología , Masculino , Corteza Prefrontal/metabolismo , Corteza Prefrontal/fisiopatología , RatasRESUMEN
Using the model of bilateral photothrombosis of the blood vessels in the prefrontal cortex we have shown that new hybrid proteins derived from recombinant human erythropoietin, carbamylated EPO-Fc and EPO-TR fusion proteins, injected intraperitoneally 1 h after ischemic injury contribute to restoration of passive avoidance response formed before photothrombotic injury and reduction in the volume of the ischemic focus. These data attest to nootropic and neuroprotective activities of these hybrid proteins. Carbamylated glycopeptide derivative ÐPO-TR exhibited prolonged neuroprotective properties.