Antibody cuts brain damage in strokes

THE discovery of an antibody that binds to certain brain receptors could reduce the side effects of a common stroke drug and buy additional time in which to use it.

The preferred treatment for ischaemic stroke, in which a blood clot cuts off the blood supply to brain tissue, is a drug called rtPA, which dissolves the clot. However, that drug has to be given within the first few of hours of a stroke, otherwise the risks of treatment outweigh the benefits. Dissolving the clot can lead to a sudden rise in blood pressure, increasing the chance that a blood vessel will rupture and bleed into the brain.

Only 5 to 10 per cent of people who suffer a stroke make it to hospital early enough to be treated with rtPA, says Denis Vivien of the University of Caen Basse-Normandie in France. The rest are given drugs that do not destroy the initial clot but reduce the chance of further clots forming.

One reason for a delay in administering rtPA is that a brain scan must be carried out to determine the nature of the stroke. People with haemorrhagic stroke, in which a blood vessel in the brain bursts, should not receive rtPA as it increases the risk of bleeding.

Now a startling discovery by Vivien has put a different perspective on this relatively simple picture: rtPA is actually released by brain cells. "This was completely unexpected," he says.

In small quantities, rtPA binds to brain-cell receptors for a chemical called NMDA. This triggers a short-lived influx of calcium, enhancing learning and memory. But damaged neurons release rtPA in large quantities, and this can cause neighbouring neurons to die. High levels of rtPA can also damage the blood-brain barrier, which may explain why the drug sometimes triggers dangerous bleeding.

Vivien has also developed an antibody that could overcome these problems. It stops rtPA from binding to the NMDA receptors, blocking its negative effects. When mice were injected with the antibody on its own or in combination with rtPA, the amount of brain damage resulting from a stroke was reduced by up to 70 per cent - both when the antibody was given immediately after the stroke and 6 hours later. Three months later, these mice also showed significantly less disability.

"With the antibody, we completely prevent the deleterious effect of rtPA and we can increase the time window during which it can be given," says Vivien, who presented his results at the Forum of European Neuroscience in Amsterdam, the Netherlands, this week. If the results are replicated in humans, this might mean that the antibody could be given on its own, even before a stroke sufferer reaches hospital. The antibody could also make it safer to administer rtPA for a much longer period, vastly increasing the number of people who could benefit from it.

What's more, because the antibody blocks the effects of the rtPA being released by damaged brain cells, the treatment might benefit people who have had a haemorrhagic stroke. "We can postulate that maybe all stroke patients could benefit," says Vivien, who is now working with a pharmaceutical company to take the antibody into clinical trials.

We suggest that maybe all stroke patients could benefit from receiving this antibody

Resting brain activity shows up damage

Studying brain activity at rest could help assess the extent of damage caused by strokes.

Imaging techniques can highlight large areas of damage, but disabilities seen in people who have had a stroke suggest that more brain regions have been affected than are picked up by scans.

To better pinpoint damage, Maurizio Corbetta of Washington University in St Louis, Missouri, used functional MRI to scan the brains of 23 stroke patients. He measured resting state activity in networks of neurons involved in controlling arm movements and directing visual attention. He then correlated these patterns with the extent of each person's disabilities.

Corbetta found that the coordination between these networks was disrupted in those who have had strokes compared to healthy individuals, even though the regions themselves showed no obvious structural damage.

"For the first time we can assess the damage to brain networks in areas that otherwise appear normal on a scan," says Corbetta, who presented his results at the Forum of European Neuroscience in Amsterdam, the Netherlands, this week. He now plans to see whether this activity can be used to predict how well people will recover from a stroke.