ABSTRACT
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.
Subject(s)
Brain-Derived Neurotrophic Factor/metabolism , Erythropoietin/metabolism , Nanoparticles/therapeutic use , Nerve Growth Factor/metabolism , Stroke/drug therapy , Animals , Brain-Derived Neurotrophic Factor/biosynthesis , Cerebral Cortex/drug effects , Cerebral Cortex/metabolism , Cerebral Hemorrhage/drug therapy , Cerebral Hemorrhage/mortality , Cyanoacrylates/chemistry , Drug Delivery Systems/methods , Enbucrilate , Hematoma/drug therapy , Hematoma/mortality , Hippocampus/drug effects , Hippocampus/metabolism , Humans , Male , Nanoparticles/chemistry , Nanoparticles/metabolism , Nerve Growth Factor/biosynthesis , Neuroprotective Agents/metabolism , Neuroprotective Agents/therapeutic use , Rats , Rats, Wistar , Recombinant Proteins/metabolism , Recombinant Proteins/therapeutic use , Stroke/mortalityABSTRACT
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.
