Researchers locate cause of brain swelling after trauma

A team of UBC researchers has discovered a potential way to stop the brain from swelling after head trauma.

Collaboration between pharmacological and molecular researchers has lead to a discovery five years in the making. A group of UBC researchers have located a channel through which chloride flows into cells after trauma. This chloride flow causes brain swelling, known as brain edema.

“It’s been known for 30 years that sodium chloride accumulation in nerve cells leads to swelling,” said the study’s personnel supervisor and UBC psychiatry professor, Brian MacVicar. “We want to understand how nerve cells can swell and what’s the key pathways by which the sodium chloride can come in.”

The team tested several different genes to locate the principle pathway. The cells of a rodent brain stopped swelling when the team halted the expression of a particular gene. As a result, a single protein was identified as a chloride channel.

“We made a tiny, little fragment of RNA that would hybridize [or] compliment the strand that was required to make a protein,” said Terrance Snutch, director of Snutch Lab and also collaborated with MacVicar. “[This RNA] hybridizes to the target to make the channel and block it from being translated into protein.”

The discovery marks a significant achievement in research on brain swelling. As human brains possess the same gene as the rodents', the next step will involve determining whether this channel can be blocked in cultured, human cells. When the head experiences trauma the brain’s position or blood flow can be disrupted, which leads to chloride flow and swelling. The skull doesn’t leave swelling anywhere to go, so the breathing centres of the brain may be crushed.

The detrimental affects of brain swelling are worsened by the fact that there are relatively few treatment options at present. When the breathing centres are in danger of being crushed, the last resort is removing part of the skull to allow the brain to swell.

“There’s very limited treatments,” said Snutch. “Even if the swelling happens, is allowed to happen, the nerve cells subsequently die afterwards so you’d be left with a lot of longer term nerve damage.”

While this discovery may look like a desirable alternative, there is a long way to go before the approach to treating trauma patients changes substantially.

“We still have a lot of questions about how the chloride current is turned on and questions like that,” said MacVicar. “The big question is, try to find safe drugs that’ll block that chloride channel, and if we can find those safe drugs then we will be able to treat brain edema.”