Intracerebral hemorrhage (ICH) is a devastating subtype of stroke with a high mortality rate, for which there currently is no effective treatment. A perihematomal edema caused by an intense inflammatory reaction is more deleterious than the hematoma itself and can result in neurological deterioration and death. Ceria nanoparticles (CeNPs) are potent free radical scavengers with potential for biomedical applications. As oxidative stress plays a major role in post-ICH inflammation, we hypothesized that CeNPs might protect against ICH. To test this hypothesis, core CeNPs were synthesized using a modified reverse micelle method and covered with phospholipid-polyethylene glycol (PEG) to achieve biocompatibility. We investigated whether our custom-made biocompatible CeNPs have protective effects against ICH. The CeNPs reduced oxidative stress, hemin-induced cytotoxicity, and inflammation in vitro. In a rodent ICH model, intravenously administered CeNPs were mainly distributed in the hemorrhagic hemisphere, suggesting that they could diffuse through the damaged blood–brain barrier. Moreover, CeNPs attenuated microglia/macrophage recruitment around the hemorrhagic lesion and inflammatory protein expression. Finally, CeNP treatment reduced the brain edema by 68.4% as compared to the control. These results reveal the great potential of CeNPs as a novel therapeutic agent for patients with ICH. [Figure not available: see fulltext.].
Bibliographical noteFunding Information:
This work was supported by grants of the followings: The Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), the Ministry of Health & Welfare, Republic of Korea (No. HI14C0211), Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (No. NRF-2015R1A2A2A 01007770), and the Institute for Basic Science (IBS), Republic of Korea (No. IBS-R006-D1).
© 2017, Tsinghua University Press and Springer-Verlag Berlin Heidelberg.
- biomedical application
- ceria nanoparticles
- free radical injury
- intracerebral hemorrhage
- neuroprotective agents
ASJC Scopus subject areas
- Condensed Matter Physics
- Atomic and Molecular Physics, and Optics
- Materials Science(all)
- Electrical and Electronic Engineering