Nanoparticle-based in vivo investigation on blood-brain barrier permeability following ischemia and reperfusion

Abstract

The blood-brain barrier (BBB) represents a significant impediment to a large variety of central nervous system-active agents. In the current study, we applied fluorescent polystyrene nanospheres (20 nm) to study the BBB permeability following cerebral ischemia and reperfusion. A microdialysis probe was implanted in the cerebral cortex of an anesthetized rat injected with fluorescent polystyrene nanospheres. The circulating nanospheres extravasating to the brain extracellular fluids were collected by the probe. Fluorescence intensity in the microdialysates throughout the course of cerebral ischemia/reperfusion was measured. Cerebral ischemia and reperfusion induced transient accumulations of extracellular nanospheres in the brain. The accumulation of nanospheres may result from their extravasation from the blood vessels. The concurrent cerebral oxygen levels monitored using oxygen-dependent quenching of phosphorescence decreased following ischemia and returned to their original levels after reperfusion. In conclusion, we demonstrated that high temporal resolution measurements of BBB permeability in vivo can be obtained using fluorescence polystyrene nanospheres and that these data correlate with changes of cerebral oxygen concentration. This present investigation indicates that nanoparticles have potential clinical applications involving drug delivery and determination of therapeutic efficacy and on-site diagnosis.