Brian Macvicar
UBC researchers have uncovered the cause of brain swelling after trauma to the head. Published April 23 in Cell, the findings could be to prevent swelling after stroke, infection, head injury or cardiac arrest.
Brain swelling, a gradual process that becomes life-threatening within days of the injury, is caused by sodium chloride (salt) drawing water into the nerve cells. This swelling — known as cytotoxic edema — eventually kills brain cells.
“We’ve known for years that sodium chloride accumulation in neurons is responsible for brain swelling, but now we know how it’s getting into cells, and we have a target to stop it,” explains principal investigator Brian MacVicar, a Professor in the Department of Psychiatry and Co-Director of the Djavad Mowafaghian Centre for Brain Health (DMCBH), a partnership between UBC and Vancouver Coastal Health.
The team, including Terrance Snutch, a Professor in the Department of Psychiatry and Director of Translational Neuroscience at the DMCBH, developed several new technological approaches to identify the cascade of events that took place within individual brain cells as they swelled.
They then switched off the expression of different genes and were able to pinpoint a single protein — SLC26A11 — that acts as a channel for chloride to enter nerve cells. By turning off the chloride channel, the accumulation of fluid into the cells was halted, swelling was halted, and nerve cells no longer died.
Terrance Snutch
“It was quite a surprising result, because we had few indications as to what this protein did in the brain,” says Ravi Rungta, then a graduate student in the MacVicar lab and the paper’s lead author.
Though the technique used by the researchers to block swelling and cell death is unlikely to work quickly enough to mitigate swelling in the case of real head trauma, the discovery has provided a target for drug development.
“This discovery is significant because it gives us a specific target – now that we know what we’re shooting at, we just need the ammunition,” Dr. MacVicar says. “That’s what we’re doing now: looking for drugs to inhibit the chloride channel.”
This research was co-sponsored by the Canadian Institutes of Health Research, Brain Canada, Genome British Columbia, the Michael Smith Foundation for Health Research, and the Koerner Foundation.