Xenon Limits Damage In Mice After Brain Injuries

Mice given xenon after a brain injury (right column) have brain cells that look much more like those that never suffered an injury (left) than those with the same injury and a substitute gas (center). Campos-Pires et al/British Journal of Anaesthesia

Traumatic brain injury (TBI) seems like one cause of death and disability we can't do much about, besides preventing the injuries in the first place. However, the rapid application of xenon gas after an injury has been found to protect mice from much of the damage, so maybe humans are next.

Even when people have survived a serious blow to the head their problems are not over, often suffering a so-called secondary injury in the hours or days after the initial impact. Secondary injuries are less likely to be fatal, but produce physical and mental disabilities, and raise subsequent risk of dementia.

A team led by Dr Robert Dickinson of Imperial College London anesthetized 72 mice and gave two-thirds of them brain injuries. They were either given xenon or a control gas 15 minutes afterward. The mice were tested on their learning and memory two weeks after the injury, and then again after 20 months. Besides measuring the effects on their cognition, Dickinson tracked the mice until they died of natural causes.

Deliberately causing brain injuries to rodents is something even people generally supportive of animal testing might feel uncomfortable with, although attempts were made to address the obvious ethical concerns. The anesthetic was long-lasting so the pain should have passed by the time the mice woke up, and the mice had much longer lives than most test subjects.

In the British Journal of Anaesthesia Dickinson reports some remarkable effects. The mice injured and not given xenon died earlier, on average, than the other two groups, performed worse on the 20-month tests and were seen to lose brain cells in the brain's hippocampus region. They also experienced greater degradation of nerve fibers in the corpus callosum. Those given xenon were always better off than their counterparts given a control gas, and on many measures were similar to those who suffered no injury at all.

The findings are consistent with previous shorter studies on mice with brain injuries and humans after cardiac arrest. What makes this different, Dickinson said in a statement, is that “We have looked at very long-term outcomes, up to 20 months after TBI in mice. This is very rarely done in animal studies and is equivalent to following up human TBI patients until their 80s.”

As a noble gas xenon is not reactive, and the mechanism is not understood. The authors propose it inhibits the brain's NMDA receptors, which otherwise become over-activated after injury.

Xenon has yet to be tested for these purposes in humans, but is already used as a general anesthetic, for which it has passed ample safety trials. With an estimated 7.7 million people in Europe alone living with disabilities caused by TBI, a cut to secondary injuries could be enormously important.

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