The brain depends on oxygen to perform even the most basic functions. Without it, the brain quickly ceases to function. And if oxygen deprivation continues, death or permanent brain damage takes just a few minutes. Hypoxia caused by a stroke, for example, activates a specific mechanism that is protective in other organs but can be detrimental to the brain. Researchers at Maastricht University Medical Center and Maastricht University have discovered why the brain is more sensitive to oxygen deprivation, or hypoxia, than other organs.
‘The brain depends on the blood to provide it with a constant supply of oxygen. Thus disruptions to any part of the body that plays a role in blood or oxygen supply can lead to hypoxia.’’This discovery solves a long-standing mystery of the unique sensitivity of the brain to hypoxia,’ says head researcher and professor Harald Schmidt. The research results were published today in the leading scientific journal Proceedings of the National Academy of Sciences U.S.A. (PNAS).
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In most cases, a stroke is caused by a blocked artery in the brain, which deprives the brain of oxygen. To prevent brain death, the blood clot must be dissolved with an anticoagulant or removed via a catheter. Stroke victims that survive are left with detrimental symptoms, regardless of how quickly they were treated. These symptoms may include severe paralysis and speech disorders.
An enzyme was found to play a crucial and specific role during a stroke. Following oxygen deprivation, this enzyme, known as NOX4, is produced by several organs and muscles. In all investigated cases, however, NOX4 is harmless, with one notable exception: the production of NOX4 in the brain is disastrous. How this happens is now clear down to the cellular level. First, the enzyme triggers the breakdown of cells of the blood-brain barrier, which protects the brain against blood and other components. Second, NOX4 also triggers a self-destruction mechanism in neurons. This combined effect results in physical and mental problems. When the NOX4 gene is deleted or the NOX4 enzyme inhibited with drugs, the blood-brain barrier and neurons remain intact and brain damage is prevented.