Abstract: A metal oxide nanoparticle composition including a cerium oxide nanoparticle and a metal adapted to enhance the neuroprotective activity of the cerium oxide nanoparticle. The metal can include noble metals such as platinum, and rare earth metals such as gadolinium, samarium, titanium, yttrium, zirconium, and a combination thereof Another metal oxide nanoparticle composition including a cerium oxide nanoparticle and a surface modifier, such as polyethylene oxide, polyethylene imine, dextran, polylactic acid, chitosan, alginate, and a combination thereof is provided. A method of using the metal oxide nanoparticle compositions as neuroprotective agents for the inactivation of reactive oxygen species in nervous tissues is also provided. More specifically, a neuroprotective method using the metal oxides such as ceria, yttria, or mixed ceria and yttria (or any of the other referenced metal oxide nanoparticle compositions) before, during, or after an ischemic event.