Xenon gas dramatically improves head injury recovery in mice

Extraordinary results raise hope for better brain injury treatment in humans. Paul Biegler reports.

Xenon is one of the noble gases and may have a major role to play in brain injury clinical care.

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The anaesthetic gas xenon has dramatically reduced long term death and disability in brain-injured mice, prompting researchers to call for a trial in humans.

Led by trauma researcher Robert Dickinson, from Imperial College London in the UK, the team found xenon given to head-injured mice preserved memory, reduced biomarkers of trauma, and led to a more than eight-fold improvement in survival at 12 months.

Xenon is one of the so-called “noble gases” that include argon and neon, and has been touted as the perfect anaesthetic, held back chiefly by its high price tag.

The researchers have previously shown that mice given xenon after brain trauma had less bruising and better neurological outcomes for up to a month afterwards. The current study followed mice for nearly two years.

At the outset, two groups of mice had blunt force applied to their exposed brain during surgery under anaesthesia. One group inhaled xenon gas for three hours, starting 15 minutes after the injury. A third control group had the anaesthetic, but no injury.

All animals were followed up with a battery of tests that measured memory, a protein called glial fibrillary acidic protein (GFAP) that goes up in humans with traumatic brain injury (TBI), and loss of white matter which is linked to disability after TBI.

The researchers also measured secondary brain injury, which is damage next to the traumatised area caused by swelling and lack of oxygen, a major focus of prevention research.

Xenon gas led to some startling improvements.

Mice that received xenon had a nearly 40% reduction in the area of secondary injury one day post-trauma. Twenty months down the track, they had nearly intact memory – on par with uninjured mice – while injured mice deprived of xenon did much worse.

GFAP levels in brain areas linked to memory were lower in xenon mice, and they were spared nearly all the white matter loss experienced by injured animals denied xenon.

Perhaps most dramatically, at 12 months one in five injured animals that didn’t get xenon was dead, while all animals in the xenon and control groups were still alive.

The figures track the stark statistics of humans after TBI. One study found 40% of people were dead 13 years after a head injury. People aged between 15 and 54 did worst, with a death rate more than seven times that of controls.

The findings come amid intense debate over the management of head injury in sport, with concussion linked to the brain condition chronic traumatic encephalopathy (CTE) which causes memory loss, thinking problems and mental health issues.

“The finding that only a short treatment with xenon can have beneficial effects on cognition, survival, and brain damage almost two years later suggests that xenon might in future prevent cognitive decline and improve survival in human TBI patients,” says Dickinson.

An editorial summary of the article says, “this translational study suggests that xenon should be evaluated in human brain injury patients”.

It is not clear how xenon offers neuroprotection, but it may work by blocking the chemical messenger glutamate that can cause overactivity and death of brain cells after injury.

The study appears in the British Journal of Anaesthesia.

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Paul Biegler is a philosopher, physician and Adjunct Research Fellow in Bioethics at Monash University. He received the 2012 Australasian Association of Philosophy Media Prize and his book The Ethical Treatment of Depression (MIT Press 2011) won the Australian Museum Eureka Prize for Research in Ethics.
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