Stroke protection: Nanoparticles X-rayed

Undoing ischaemia

 

Ceria nanoparticles have been tested as putative agents to protect against the deleterious effects on the brain of ischaemic stroke. X-ray photoelectron spectroscopy provides the detailed clues about nanoparticle behaviour.

Stroke is commonly caused by an interruption to the blood flow to the brain (ischaemia), the sudden drop in oxygen and nutrient supply can cause severe disability as parts of the brain die and stroke is a leading cause of death in industrialized nations. Rapid medical intervention can often stave off the worst effects in some cases. As such, public awareness campaigns have been aimed at educating people in how to spot the signs of stroke so that emergency medical treatment can be administered as soon as possible. It can mean the difference between significant disability, death or a better outcome.

Biomedical research is constantly searching for new, more effective treatments that can protect the brain from the effects of stroke. Writing in the current issue of Angewandte Chemie, a research team from Korea describes how cerium oxide nanoparticles might be used to augment more common treatments by trapping the highly reactive oxygen species, such as superoxide, peroxides and hydroxyl radicals released during ischaemia and so prevent these and the other free radicals they generate from killing brain cells. Without such protection nerve connections and neurovascular units are usually at least partially destroyed by the stroke and brain function in those parts of the brain stops.

There are treatments and pharmaceuticals that can help during stroke although these are aimed more at combating thrombosis and the subsequent additional inhibition of blood flow. However, the Korean team of Seung-Hoon Lee, Taeghwan Hyeon, and their colleagues at Seoul National University suggests that their intervention might be among the first aimed at protecting nerves themselves from the oxidative damage that also wreaks havoc on brain tissues following stroke.

Cells naturally contain enzymes to help the cell deal with reactive oxygen species, among them superoxide dismutases and catalase. The former converts superoxide anions to hydrogen peroxide and the latter hydrolyses hydrogen peroxide. Cerium(III) ions can do both of these things in the absence of enzymes. Unfortunately, crystalline ceria contains mainly cerium(IV) at least in the bulk. Reduce the ceria particles to the nanoscopic scale where they are just mere nanometres in diameter and an increasing proportion of the surface of the particles will expose points at which oxygen atoms are absence. At these points, cerium(III) ions will be present that can thus bond to oxygen atoms from reactive oxygen species with which the ceria nanoparticles come into contact. That process is reversible but allows the oxygen radicals to be mopped up and for them to form less harmful species.

The team used X-ray diffraction to examine the ceria nanoparticles and X-ray photoelectron spectroscopy to confirm the oxidation state of cerium(III) sites on the particle surface.

To test the idea, the team boosted the concentration of reactive oxygen species in a cell culture; immediately cells begin to die in the culture. However, ceria nanoparticles quickly added to the brew drastically improved the cell survival rate, the team says. They have also demonstrated that the process can reduce the stroke volume, the amount of dead brain tissues as well as lessening nerve damage in a rat model of ischaemic stroke. The team points out that it is a fine line to optimisation of the dose and time for the most effective treatment with the nanoparticles.

Self-targeting

There is one intriguing, almost chance, aspect of how the ceria nanoparticles are taken up by the brain following stroke in the animal model. The team found that concentrations were lowest in the unaffected, healthy parts of the brain, but were drastically elevated in the ischaemic regions. This, they suggest, is because the nanoparticles cannot normally pass through the blood-brain barrier, but when that has been damaged, as occurs in stroke the nanoparticles can breach it relatively easily and so get to the parts of the brain where oxidative damage is occurring.