RESUMO
Human recombinant erythropoietin adsorbed on poly(butyl)cyanoacrylate nanoparticles and administered intraperitoneally in a dose of 0.05 mg/kg exhibited a neuroprotective effect in experimental intracerebral posttraumatic hematomas (hemorrhagic stroke) and reduced animal mortality. Human recombinant erythropoietin, native and adsorbed on lactic and glycolic acid copolymer-based nanoparticles, exhibited no antistroke effect on this model. Analysis of reverse transcription PCR products showed that human recombinant erythropoietin adsorbed on poly(butyl)cyanoacrylate nanoparticles more than 2-fold increased the expression of BDNF and NGF neurotrophins in the rat brain frontal cortex and hippocampus.
Assuntos
Fator Neurotrófico Derivado do Encéfalo/metabolismo , Eritropoetina/metabolismo , Nanopartículas/uso terapêutico , Fator de Crescimento Neural/metabolismo , Acidente Vascular Cerebral/tratamento farmacológico , Animais , Fator Neurotrófico Derivado do Encéfalo/biossíntese , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Hemorragia Cerebral/tratamento farmacológico , Hemorragia Cerebral/mortalidade , Cianoacrilatos/química , Sistemas de Liberação de Medicamentos/métodos , Embucrilato , Hematoma/tratamento farmacológico , Hematoma/mortalidade , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Humanos , Masculino , Nanopartículas/química , Nanopartículas/metabolismo , Fator de Crescimento Neural/biossíntese , Fármacos Neuroprotetores/metabolismo , Fármacos Neuroprotetores/uso terapêutico , Ratos , Ratos Wistar , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/uso terapêutico , Acidente Vascular Cerebral/mortalidadeRESUMO
The neuroprotective activity of recombinant human erythropoietin (rhEPO) loaded poly(lactic-co-glycolic) acid (PLGA) nanoparticles has been observed in rats with model intracerebral post-traumatic hematoma (hemorrhagic stroke). It is established that rhEPO-loaded PLGA nanoparticles produce a neuroprotective effect in rats with hemorrhagic stroke, which is manifested by reduced number of lethal outcomes and animals with neurological disorders. Treatment with rhEPO-loaded PLGA prevented amnesia of passive avoidance reflex (PAR), which was produced by the hemorrhagic stroke, and reduced the area of brain damage caused by the intracerebral hematoma. These effects were recorded during one-week observation period. Native rhEPO exhibited a similar, but much less pronounced effect on the major disorders caused by the model hemorrhagic stroke in rats.
Assuntos
Amnésia/prevenção & controle , Hemorragia Cerebral Traumática/tratamento farmacológico , Eritropoetina/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Hemorragia Cerebral Traumática/mortalidade , Hemorragia Cerebral Traumática/fisiopatologia , Modelos Animais de Doenças , Portadores de Fármacos/química , Eritropoetina/administração & dosagem , Humanos , Ácido Láctico/química , Masculino , Nanopartículas/química , Fármacos Neuroprotetores/administração & dosagem , Tamanho da Partícula , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Ratos , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/uso terapêutico , Taxa de SobrevidaRESUMO
The neuroprotective activity of recombinant human erythropoietin (r-HuEpo) sorbed on poly(butyl)cyanoacrilate nanoparticles (EPO-PBCA) and on polylactic-co-glycolic acid nanoparticles (EPO-PLGA) has been studied on Wistar rats with intracerebral post-traumatic hematoma (model of hemorrhagic stroke) (IPH-HS) in comparison to native r-HuEpo. It is established that EPO-PBCA produced a protective effect in rats after IPH-HS that was manifested by a decrease in the number of animals with neurological disorders such as circus movement, paresis, and paralysis of hind limbs; the drug also improved coordination (rotating rod test), reduced the number of lost animals, and decreased the loss weight among survived rats. In addition, EPO-PBCA optimized the research behavior of rats with IPH-HS in the open field test and prevented amnesia of passive avoidance reflex (PAR), which was caused by the IPH-HS. These effects were manifested during a two-week observation period. EPO-PLGA has a similar but much less pronounced effect on the major disorders caused by IPH-HS. The efficiency of native r-HuEpo as a neuropotective agent was insignificant and only manifested by decrease in the number of lost animals with IPH-HS.