Abstract 15309: Newly Designed Ceria Nanoparticle for the Therapy of Ischemic Stroke
Objective: No reliable neuroprotective therapy for ischemic stroke has been identified for clinical practice. Ceria nanoparticles are known to exhibit potent free radical scavenging activity. In this study, we investigated the therapeutic effect of newly designed ceria nanoparticles for experimental ischemic stroke.
Methods: We made ceria nanoparticles via the combining process using thermal decomposition and reverse micelle method. We induced ischemia-reperfusion injury in SD rats, and ceria nanoparticles was administered intravenously. Infarct volume and the number of TUNEL-positive apoptotic cells were measured at 24 hours. To identify the anti-oxidant effect of nanoparticles, hydroethidine was administered 15 minutes before inducing focal ischemia, and oxidized hydroethidine was detected at 3 hours using fluorescent microscopy. To identify anti-apoptotic effect, pro-apoptotic proteins were detected via Western blot analyses.
Results: We acquired discrete and uniform 3 nm-sized ceria nanoparticles and PEGylated nanoparticles are highly dispersible and biocompatible. Low-dose ceria nanoparticles (0.1 and 0.3 mg/kg) did not decrease infarct volumes, whereas ceria nanoparticles at concentrations of 0.5 and 0.7 mg/kg considerably reduced infarct volumes up to 50% of those of the control group (p<0.05). Quantitative analysis showed that the number of TUNEL-positive cells was remarkably decreased in the ceria-injected group (274±36 cell/mm3 vs. 82±5 cells/mm3; p<0.05). Oxidized hydroethidine signals were weakly observed in the ischemic cortices of ceria-injected group compared with control. Pro-apoptotic proteins such as phospho-p53, cleaved caspase-3, and gelsolin decreased in the ceria-injected group (p<0.05).
Conclusion: We demonstrate that ceria nanoparticles protect against ischemic stroke in living animals. These results suggest that ceria nanoparticles are promising therapeutic agents for ischemic stroke.
- © 2012 by American Heart Association, Inc.