Bright nanoparticles shine light on treating brain injuries
Traumatic brain injury is one of the most common causes of death, especially among children and young adults. Injuries can occur through a hit on the head, or by sudden movements that shake the brain within the skull. One reason they are so common is that they can happen in numerous situations, from a simple fall through to a car accident. “The brain is encapsulated in a kind of box,” explains NEUROTARGET project coordinator Nikolaus Plesnila, professor of Experimental Stroke Research at the Ludwig-Maximilians University of Munich, Germany. “This means that there is little space for it to expand. When this happens after an injury, there is a risk that blood vessels will be compressed, stopping blood flow to the brain. This can cause death.” For neuroscientists, understanding what is going on in this encapsulated space without opening it up remains a key challenge. The progression of brain injuries is also difficult to predict. Some patients will suffer no long-lasting damage; others can experience slowed speech and mood changes later in life.
Bright idea
One area of clinical interest in the treatment of traumatic brain injuries is the use of nanoparticles to deliver drugs directly to the brain. A key advantage is that these tiny particles are able to cross the blood-brain barrier, a membrane of cells that tightly regulates which molecules reach the brain. “There is not that much known about how this works though,” says Marie Skłodowska-Curie Actions fellow Igor Khalin, researcher at Ludwig-Maximilians University of Munich. “We know about the drug we are injecting and can see if this has an effect on neuron cells. But what actually happens in between? How does the blood-brain barrier work?” To answer this, the NEUROTARGET project developed new techniques to help neuroscientists see what is happening in the brain. Khalin combined the expertise of Plesnila’s neurological lab with the latest research in biophotonics. “My idea was to bring these two areas of research together,” he explains. “I wanted to take hollow nanoparticles and fill them with bright, biophotonic material.”
Crossing the barrier
Once injected into the tissue, the team was able to follow the nanoparticles as they crossed the blood-brain barrier. “Igor’s technique works like a torch in the woods at night,” notes Plesnila. “From far away, the source of light looks huge. When you get closer you realise that the torch is actually small. It is just the halo of light that you see.” While the nanoparticles are too small themselves to be seen under a conventional microscope, neuroscientists can follow the light they emit using two-photon fluorescence. “For the first time, we have shown how it is possible to follow these tiny nanoparticles,” says Plesnila. This ability to track nanoparticles from injection through to the brain opens up huge opportunities. For example, neuroscientists can use the technique to assess when and where the most effective means of injection is, and to better understand the behaviour of the blood-brain barrier. “Next steps include translating these results to the clinical environment,” adds Plesnila. “We want to load these particles with drugs, to understand how we can more precisely target brain injuries. These will hopefully lead to better treatments.” Plesnila and his team are also looking into using biocompatible, biodegradable nanoparticles, which would dissolve in the body naturally after they have delivered drugs.
Keywords
NEUROTARGET, nanoparticles, brain, skull, injury, biophotonics, neuron, neurological
