One of the biggest dangers from serious head injuries isn鈥檛 always the initial damage, but an after-effect that occurs in the following hours and days, when excess fluid builds up in the brain, compressing nerve cells.
Now, a study in mice suggests that a cocktail of three drugs, already used for high blood pressure, can ease this fluid build-up and improve recovery after a blow to the head.
It has long been known that after a brain injury, there can be a rise in blood levels of a hormone called noradrenaline (known as norepinephrine in the US), which is involved in the 鈥渇ight or flight鈥� response. Higher levels of noradrenaline correlate with worse long-term brain damage, although it was unclear if the hormone surge was causing this or was an effect of it.
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In the latest research, at the University of Rochester in New York and her colleagues have shed light on why noradrenaline levels are so important and found a possible way of averting that related damage.
It is based on Nedergaard鈥檚 discovery, made about a decade ago, that the brain contains a 鈥渨aste disposal system鈥�. More properly known as the glymphatic system, this is a network of fine tubes that pumps fluid that contains metabolic waste from the head.
In people without brain injuries, noradrenaline seems to play a crucial role in turning the drainage system on and off. The system usually functions at very low levels in the day, when noradrenaline levels are relatively high, but ramps up at night, when levels are low. 鈥淵ou can only do your housekeeping function when you鈥檙e asleep because the brain is so busy during daytime,鈥� says Nedergaard.
She wondered if the surge of noradrenaline after head injuries puts the brain into a permanent state of high alert, suppressing the usual night-time drainage process and causing the harmful build-up of fluid.
Her team tested this idea by giving mice that had experienced a blow to the head either a placebo or a mix of three drugs that are known to suppress noradrenaline activity.
The animals given the drug cocktail had less brain swelling in the first 3 hours after their injury than those that got a placebo. They also recovered better from their injury over the following two weeks, judged by how far they could walk along a narrow beam.
The strategy needs to be tested in people, but the fact that the three drugs are already known to be safe for treating high blood pressure should make it easier to get trial approval, says Nedergaard. They could also have potential for treating stroke, which can similarly cause brain swelling, she says.
鈥淚f this leads to a better treatment [for brain injuries] it could be very significant,鈥� says at Trinity College Dublin, Ireland. 鈥淲e can often handle the initial injury, but not the secondary damage.鈥�
at the University of Cambridge says the approach looks promising, but adds that doctors who treat people with brain injuries first need a quick and simple way of measuring glymphatic activity at the bedside, which can currently only be done via time-consuming brain scans.
Nature
