TCD research makes big brain breakthrough

SWELLING IN THE brain is not good news, and can be difficult to treat. But new research from Trinity College Dublin has demonstrated a way to help relieve the pressure that could pave the way to better treatments.

Swelling after traumatic brain injury is similar to what would happen if a pipe burst in a house with its windows and doors close. As the water levels rise, without enough routes of escape, the damage is immense. In the brain, swelling and fluid build-up can increase pressure inside the skull and the damage can be fatal.

Current treatments include using sugar solutions to try and draw fluid back into the bloodstream or in some cases even removing part of the skull – effectively taking the roof off the house.

But the new study, published last week in Nature Communications, managed to reduce cerebral oedema, or fluid accumulation, by allowing fluid to escape into the bloodstream.

Using a mouse model, they injected molecules of small interfering RNA into blood vessels that feed the brain. The siRNA was designed to interfere with a protein called claudin-5, which forms part of the blood-brain barrier, a tightly knit protective arrangement of cells lining blood vessels in the brain.

Modulating this barrier – which is like opening the windows slightly in the house – allowed fluid to drain from the swollen region of the brain into the bloodstream. “Our system seems to work by keeping the blood-brain barrier marginally open to allow for the increased fluid within the brain to simply drain across concentration gradients back into the blood,” says researcher Dr Matthew Campbell from the Ocular Genetics Unit at TCD. “As the blood is flowing through the vessels in the brain, this excess water is taken away.”

The study received funding from the US Department of Defense and Enterprise Ireland.

There are plans to start human trials next year to target cerebral oedema formation in patients who have suffered an out-of-hospital cardiac arrest, says Dr Campbell.

“Generally, the prognosis for these individuals is very poor, and we are currently undertaking clinical research with Dr Colin Doherty in St James’s Hospital to identify patient cohorts to recruit to our clinical trial next year.”

– Claire O’Connell