Intravenous administration of retinoic acid-loaded polymeric nanoparticles prevents ischemic injury in the immature brain

Abstract

Perinatal stroke is often difficult to diagnose and an established treatment has not yet been validated, except for symptomatic measures. Herein, we propose to test the neuroprotective potential of the intravenous injection of retinoic acid-loaded nanoparticles (RA-NP) upon ischemic injury to the immature brain. The role of RA-NP on endothelial cells and organotypic slice cultures exposed to oxygen and glucose deprivation was assessed by evaluating markers pertaining to survival, proliferation, oxidative stress (NO, ROS), neuronal damage (enolase), vascular oxidation (p47phox) and microglia activation (CD68). Data showed that RA-NP (3 μg/ml) increased endothelial proliferation and survival, and normalized NO and ROS levels. The intravenous administration of RA-NP (10 μg/g) prevented ischemic injury in the hippocampus of 2-day-old mice by inhibiting cell death and normalizing markers of neurovascular function and inflammation. In sum, systemic administration of RA-NP protected neurovascular integrity and the inflammatory milieu from ischemia in the immature brain, highlighting its therapeutic value for perinatal stroke.