Scientists have for the first time identified the sequence of events that happen in the brain when the organ shuts off and we die.
They discovered what they call the ‘wave of death’ – a flood of chemicals sweep through the brain, followed by a wave of electricity, then nothing.
Lead author Séverine Mahon, a neuroscientist at the Paris Brain Institute in France, told DailyMail.com: ‘Our work shows that dying (and not death) is not an event but a ‘long’ process that can be reversed up to a certain point.’
‘But we don’t yet know exactly where the point of no return lies.’
Death happens in stages. It’s not as simple as flipping a switch on and off. In multiple phases, waves of chemical and electrical activity wash over the brain before all function ceases
To investigate what the process of death looks like in the brain, the team surgically implanted tiny probes to groups of brain cells and individual neurons in the brains of rats.
These tools measured the electrical and chemical activity in the rats’ brains as they died.
Their results show how death is not as simple as we may think.
It’s not just a switch flipping from ‘on’ to ‘off,’ but a step-by-step process of cells and regions shutting down in different ways and emitting unique signals as they do.
The exact ‘point of no return’ – when our consciousness shuts off and cannot return – is still up for debate, but understanding how and where the ‘wave of death’ occurs can help doctors develop better drugs or treatment strategies to prevent brain damage in the event of a serious injury, said the researchers behind the new work.
There are rough time windows when a dying brain can be resuscitated, but not a hard-and-fast cutoff point, recent research has shown.
Restoring breathing soon enough can reverse the brains shutdown process, enabling neurons to begin firing again. But some cells are more sensitive than others and will die sooner if not resuscitated
In the new study, anesthetized animals were taken off mechanical ventilators while the implanted instruments recorded what was happening, both as the animals died and as they were brought back to life.
Activity was assessed in the somatosensory cortex, a region on the brain’s outer layer that processes signals about temperature, touch, texture, and pain, as well as awareness of the body’s location and movement in space. Our brain’s somatosensory cortex has a similar role, structure, and location.
As the rats died, scientists observed the first wave of activity, caused by the chemical messenger glutamate that encourages neurons to fire.
Massive glutamate release happened as the brain cells, deprived of oxygen, quickly used up their supply of ATP, the molecule that gives cells the energy they need to function.
And right before the brain flatlines, there comes ‘a period of intense cortical activity,’ Mahon said.
That surge takes the form of gamma and beta waves – brain signals that are usually linked with conscious experiences.
‘We know that these brainwaves in healthy subjects are responsible for memory recall,’ Ajmal Zemmar, a neurosurgeon at the University of Louisville who was not involved in the research, told DailyMail.com.
‘So we are wondering if at the time of death, perhaps the same thing happens: that you have a memory recall after your heart stops beating and the brain prepares to undergo death.’
Yet the patient is clearly unconscious when this happens, Mahon said.
Some believe that this activity is responsible for the near-death experiences people report, she added.
‘An alternative hypothesis (ours) is that near-death experiences occur during the gradual return of cortical activities (which resemble those associated with hallucinations) after successful resuscitation.’
Unfortunately, it is difficult or impossible for scientists to know exactly how each part of the dying experience feels.
‘Once someone dies, you can not ask them,’ Zemmar said.
After these mysterious waves of activity, brain activity goes flat. But that’s not the end.
This is when the so-called ‘wave of death’ happens: A powerful wave of electricity radiates through the brain as neurons shut down.
That electrical wave, called ‘anoxic depolarization,’ signals the death of the neurons.
‘Like a swan song, it is the true marker of transition towards the cessation of all brain activity,’ said study first author Antoine Carton-Leclercq, a graduate student, in a statement.
‘We already knew that it is possible to reverse the effects of anoxic depolarization if we manage to resuscitate the subject within a specific time window,’ Carton-Leclercq said. ‘We still had to understand in which areas of the brain the death wave is likely to do the most damage to preserve brain function as much as possible.’
When scientists restored oxygen and bloodflow to rats’ brains, the wave of death reversed and activity began again
By comparing the electrical activity before and during anoxic depolarization, they found that the wave of death began in the cells deep in the somatosensory cortex – but still relatively close to the surface of the brain as a whole – called layer 5.
It fanned both upward to the surface and downward into even deeper layers.
‘We have observed this same dynamic under different experimental conditions and believe it could exist in humans,’ Mahon said.
The fact that the wave of death originated in layer 5 suggests that these particularly energy-hungry cells may be cut loose sooner by the brain, hypothesized Zemmar, as it tries to preserve more important regions – like cortical layer 2, which is associated with thinking.
To find out whether brain function can be recovered, they turned the rats’ ventilators back on and continued to record electrical activity in multiple brain layers.
When the dying brains were brought back to life, the neurons repolarized – the opposite of what happened during the wave of death.
As neurons repolarized, the team found that they produce brainwave signatures that indicated how likely it was that this sensitive organ would recover function.
‘It is now established that, from a physiological point of view, death is a process that takes its time,’ said lead researcher Stéphane Charpier, ‘and that it is currently impossible to dissociate it rigorously from life.’
In other words, the wave of death does not necessarily mean that the brain is all the way dead.
‘We now need to establish the exact conditions under which these functions can be restored and develop neuroprotective drugs to support resuscitation in the event of heart and lung failure,’ Charpier added.
In most cases in people, restoring breathing within four minutes of the heart stopping will prevent brain death.
After that, different areas begin to die at different rates – just like in the rats.
If doctors can figure out how to prevent the wave of death, either by targeting the origin of the wave or by limiting its spread, they can help slow or stop this process.
The new study is just the beginning of this search, but finding the source of the problem is the first step toward solving it.
The results appeared in the journal Neurobiology of Disease.
