Brain damage mechanism discovered

Researchers in the Netherlands have discovered why oxygen deprivation to the brain during a stroke has such catastrophic effects.

A team from Maastricht University Medical Centre and Maastricht University, writing in the journal Proceedings of the National Academy of Sciences, has identified a single enzyme that is produced after oxygen deprivation which causes severe damage to tissues – but only in the brain.

The enzyme, NOX4, is produced by several organs and muscles when they undergo oxygen deprivation, or hypoxia. However, in all these instances it is harmless.

The Maastricht team, led by Harald Schmidt, discovered that NOX4 in the brain behaves very differently. As soon as it is produced it triggers the breakdown of cells at the blood-brain barrier. It also kicks off a self-destruct mechanism in neurons. Combined, these actions result in profound physical and mental damage.

In experiments, Schmidt’s team found that if the NOX4 enzyme was eliminated – either by inhibiting it with drugs or removing the gene responsible for creating it – both the blood-brain barrier and neurons remained intact, and no brain damage resulted.

“This discovery solves a long-standing mystery of the unique sensitivity of the brain to hypoxia,” says Schmidt.

Understanding the role of NOX4 now presents new targets for post-stroke treatments and rehabilitation, he adds.