Traumatic brain injury (TBI) has been a major thorn in the side of neuroscientists for some time, and has proved extremely difficult to both detect and treat. Regularly suffered by military personnel and NFL stars, the condition is often not picked up by standard brain imaging techniques, although as detection methods improve, scientists are getting ever closer to gaining the upper hand on this invisible killer. Now, researchers have announced the development of a compound that is able to bind to the site of brain injuries, opening the door to the delivery of wound-healing drugs.
Outlining their research in the journal Nature Communications, the study authors explain how injuries tend to provoke the development of scar tissue within the brain. Preventing this from happening is very tricky, since any drugs that could stop these scars from forming tend to be washed out from the brain by blood flow very soon after they are administered, meaning they don’t stay in place long enough to have an effect.
Crucially, though, these scars are known to contain high concentrations of a protein complex called chondroitin sulfate proteoglycans (CSPGs). The researchers therefore attempted to create a compound capable of binding to CSPGs, which could be used to carry drugs to the site of injuries and ensure they remain in place long enough for healing to occur.
The molecule they created is a peptide consisting of four amino acids, called CAQK. To test out its efficacy, the researchers inflicted two different types of brain injury on mice. The first type – known as penetrating brain injury – was designed to mimic the sorts of lesions suffered when bullets and other shrapnel enter the brain, while the other was more similar to TBI, which normally occurs as a result of being hit on the head with a blunt object.
They then filled nanoparticles with drugs and coated them with CAQK, using the peptide like a kind of Trojan horse, entering the brain and binding to the site of the injury, before releasing its contents from within.
Image: Football players face a comparatively high risk of suffering from TBI. Action Sports Photography/Shutterstock
Unfortunately for the mice, the researchers didn’t actually use wound-healing drugs in this instance. Instead, they stained the rodents’ brains with a fluorescent marker and filled the nanoparticles with gene-silencing RNA capable of turning off this fluorescence. In doing so, they were able to visibly verify that the nanoparticles had reached their target and had the desired effect.
In their write-up, the researchers reveal the experiment to be a huge success for both types of brain injury, with CAQK enabling the nanoparticles to remain at the site of the injury for five days. Importantly, they were then able to repeat this achievement using human cells in the laboratory, as well as slices of human brains, proving that the CSPG target is not exclusive to mice and that this same technique can therefore be used to treat TBI in people.
TBI is normally caused by blows to the head, and can manifest itself in a number of ways, including headaches and memory deficits. Oleg Golovnev/Shutterstock