PBCA-mediated neurotrophin-3 and hypoxia response element delivery in the treatment of rats with hemorrhagic stroke

Hypertensive ICH is a rapidly evolving process which causes necrotic cell death followed by apoptotic cell death, and alters some gene expression levels in the surrounding tissue area of brain injury. The blood-brain barrier (BBB) limits the penetration of substances into the brain, and the development of intravenously administered carriers for controlled release of gene vector has been an ambitious challenge. It has been concluded that polybutylcyanoacrylate (PBCA) nanoparticles (NPs) could successfully deliver protein across the BBB. In this study, we construct a Neurotrophin-3 (NT-3) expression plasmid containing the HRE and a CMV promotor. It is applied to activate the HIF-1/HRE system of gene regulation and used to produce NT-3 proteins after ICH. The data indicate that the PBCA NPs/NT-3-HRE complexes are very low toxicity. The PBCA NPs can protect cmvNT-3-HRE from degradation and sustain across the BBB in vitro, and enhance the NT-3 protein expression after hemorrhagic stroke with PD treatment. Moreover, the disrupted BBB and impaired neurons can be revived by PD treatment after ICH. In conclusion, the PBCA NPs justified as an appropriate system for gene delivery in the brain because of it possibly influences therapeutic outcome of ICH in the rats.