Nanoparticles Improve the Passage of Nerve Growth Factor Through Blood-Brain Barrier by Stimulating Aβ Clearance

Abstract

Nerve growth factor (NGF) is critical for peripheral ganglion cell survival. However, it cannot penetrate blood-brain barrier (BBB). Therefore, a carrier system is required to enhance its transport across BBB. First, the ultrastructure and permeability of BBB from mice modeled by NGF nanoparticle treatment were evaluated by electron microscopy. The influx of NGF into brain was then observed using laser spectroscopy and immunofluorescence. Finally, learning and memory abilities were assessed, and hippocampal cell apoptosis was assessed using fluorescent TUNEL staining. NGF nanoparticles (NPs) induced enhanced permeability of BBB, indicating that NGF NPs can enhance BBB permeability. In NGF nanoparticle group, FITC-NGF showed significant vascular infiltration, but not in control and model groups. NGF NPs stimulated Aβ scavenging ability to promote NGF passage through blood vessels. Compared with control group, NGF NPs group had a longer distance to find the platform on day 5 and a longer incubation period. And apoptosis in NGF nanoparticle group was lower than control group. NGF NPs can induce NGF to enter brain probably by increasing the permeability of BBB. NGF NPs can be used as a new strategy to deliver therapeutic drugs to the central nervous system.