Scientists say they have discovered the exact mechanism behind the death of brain cells following a stroke.
Dying nerve cells cannot remove excess calcium, say the scientists
The main culprit is an overload of charged calcium particles or ions, they told the journal Cell.
As the brain is starved of oxygen by reduced blood flow, events occur that cause dangerously high levels of calcium ions within the brain cells.
The Medical Research Council team believes correcting the calcium imbalance could help treat strokes.
Scientists have suspected for some time that calcium was the culprit.
But research had mainly concentrated on trying to block the entry of calcium ions into dying nerve cells.
The latest study suggests that the main problem is actually a fault in the mechanism that removes calcium ions from the nerve cells.
Professor Pierluigi Nicotera and colleagues at the MRC's toxicology unit in Leicester looked at what was happening in the brains of rats when these animals suffered a stroke.
When the blood flow to the brain was abruptly stopped, as occurs with a stroke, the nerve cells deprived of oxygen released chemicals that they use to communicate with each other.
One of these, called glutamate, causes more widespread damage by triggering a flood of calcium ions into the affected and neighbouring nerve cells.
This calcium influx then activates enzymes called calpains, which break down a protein in the nerve cell's outer membrane that would normally pump calcium out of the cell.
The result of these two insults is dangerously high calcium levels which kill off the neurons.
This could explain why stroke therapies aimed solely at decreasing calcium entry into nerve cells have been unsuccessful, said Professor Nicotera.
"The drugs conceived so far have failed in clinical trials because they only block the entry of calcium rather than helping to remove it from the cell."
He said his team were currently testing different molecules that might help nerve cells to remove the excess calcium.
"But it will be some years before we have new drugs," he said.
A spokeswoman from the Stroke Association said: "This could help to fully determine the exact mechanism behind the death of nerve cells in the brain that happens when blood supply to this area is blocked, such as in the case of a stroke.
"However, this research is only at initial stages and further work in this field is needed to fully determine whether this will lead to more effective treatments for stroke, which specifically address this mechanism."