Editorial: “A matter of life and brain death“
Chop off a rat’s head, and a minute later a wave of electrical activity passes through their brain. Is this the boundary between life and death?
WHEN people were guillotined in the French revolution, witnesses reported that sometimes the eyes on the decapitated heads would blink, or lips would twitch.
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Enthralled audiences wondered: was the victim still conscious? Such speculation about the precise moment of death has now been revived by an ethics experiment that uses the guillotine once more.
Anton Coenen, Tineke van Rijn and their colleagues at Radboud University Nijmegen in the Netherlands think their study may have pinpointed the boundary between life and death. That is a big claim, but even if it does not pan out, the research has still revealed a crucial step in the process of brain death. It also hints at ways to resuscitate patients who are currently beyond saving.
The Dutch team took healthy rats, embedded electrodes in their heads to monitor brain activity, then decapitated them. The study was carried out at the request of their university’s ethics committee to find out whether this method of killing animals is humane. Lab rats are commonly decapitated without anaesthetic for post-mortem examination, as drugs can contaminate tissue samples. Coenen’s team aimed to find out how quickly the rats lost consciousness and therefore how much they might suffer.
After decapitation, the rats’ brain activity, as measured by electroencephalogram (EEG), immediately started dropping, falling to half the pre-decapitation level within 4 seconds. Earlier studies comparing awake and sleeping rats suggest that such low activity is a good indicator of complete unconsciousness.
Nine of the 17 rats used in the study were fully conscious, while the other eight had been sedated. Before decapitation their EEG traces were quite different, but afterwards they both followed the same course. That suggests the awake rats become completely unconscious just as quickly as the sedated animals.
Coenen thinks this is good evidence that decapitation is humane, even when the rats are awake. “Killing by decapitation causes the lowest amount of suffering,” compared with other methods, he says.
“The study is good evidence that decapitating rats is humane, even when they are awake”
Reports from revolutionary France suggested that guillotine victims remained conscious for up to 30 seconds after decapitation, even blinking at their executioners to alert them to their condition. “I think it’s likely that these people had an awareness for maybe seconds,” says neurologist of the University of Kentucky in Lexington. He says the clinical evidence shows that people are completely unconscious within 10 seconds of blood flow to the brain being cut off.
But Coenen noticed something else. He kept the EEG running for several minutes after decapitation and noticed a 10-second wave of electrical activity in the rats’ brains. The wave appeared 50 seconds after decapitation in rats that had been awake, and after 30 seconds in sedated animals ().
Coenen thinks the wave could represent neurons’ electrical potentials collapsing. Healthy neurons maintain a small negative voltage, roughly 70 millivolts, across their outer membranes. They do this by pumping positive ions out of the cell, using molecular pumps in the outer membrane. When a neuron fires, the voltage temporarily flips and the cell interior becomes positively charged. This “action potential” travels along the length of the neuron and is how nerves carry signals. It can only be generated if the cell maintains its negative charge during its resting state, and this means keeping the ion pumps going.
Coenen suggests that with a loss of blood supply, the pumps run out of energy and positively charged calcium ions flood back into the neurons. This depolarisation could be responsible for the EEG wave.
This “wave of death”, Coenen says, could be a good indicator of ultimate brain death – the moment beyond which neurons cannot function, even if their energy supply is restored. Crucially, a similar wave has been seen in humans.
In 2009, Lakhmir Chawla and colleagues at the in Washington DC published case studies of the brain activity of seven critically ill patients during and after their life support machines were turned off. After the patients’ hearts stopped and their blood pressure fell, Chawla saw sharp spikes in brain activity lasting between 30 and 180 seconds ().
Like Coenen, Chawla thinks the wave could reflect neurons depolarising. His paper made after he suggested that the wave might represent a near-death experience, though he now emphasises that this was just a hypothesis.
Nelson, who has studied near-death experiences for many years, thinks they have nothing to do with the wave. Neurons depolarise en masse during severe epileptic seizures, he points out, and people who experience such seizures have no memory of them afterwards. “If all the neurons depolarise, you can’t have the neuronal patterns that cause memory,” he says.
While the wave may not create conscious experiences, it could represent an important boundary, according to neurologists contacted by Â鶹´«Ă˝. Sam Parnia of in New York thinks the wave might mark the beginning of cell death. “[Calcium ions] start damaging and killing the cells,” he says.
Nelson is more cautious about the idea that the wave is linked to cell death. “When a neuron dies it bursts like a balloon,” he says, “and there’s a complex cellular sequence that leads up to that.” No one knows how the wave fits in.
Rather than neurons giving up the ghost, the wave might actually be the brain making a last-ditch attempt to restart the heart with a powerful burst of activity, says resuscitation science at the University of Pennsylvania in Philadelphia. He compares it to a car trapped in a snowdrift: the driver tries revving the engine, but succeeds only in spinning the wheels.
“The wave might actually be the brain making a last-ditch attempt to restart the heart”
Becker suspects the wave will turn out to be a signal that the neurons have stopped functioning, rather than of irreversible damage. Still, that in itself would be a significant indicator that brain death is approaching. “The brain is screaming that something is terribly wrong,” he says.
As resuscitation techniques improve, the length of time the brain can last without blood flow grows ever longer. “I was taught that after 4 minutes without oxygen, the brain begins to have irreversible injury,” Becker says. “We now know that can’t be true.”
He points to a recent study in which researchers successfully revived pigs after 15 minutes of cardiac arrest, with no resulting brain damage (). “We don’t know what the limit is,” he says.
If Becker is correct that the wave is reversible, it could prove useful for resuscitating people who are critically ill. “In the emergency department we don’t typically put an EEG on these patients,” he says. “But this makes me think that maybe I should. It could give me the information I need to know if my therapies are working.” How well cardiopulmonary resuscitation is performed is often crucial, and doctors could improve if the EEG gave them feedback on how their methods were affecting patients’ brains.
