Previous clinical trials in humans have suggested that administering oxygen under pressure could harm stroke patients. The use of supplemental oxygen after blood flow is restored in the brain appears to actually cause harm by unleashing free radicals.

Scientists have now shown that giving supplemental oxygen to animals during a stroke can reduce damage to brain tissue surrounding the clot. The study showed that the use of pure oxygen that was delivered by mask during stroke was also effective, making for easier clinical application of such a therapy when the time for that is right.

The previous studies did not take into account the status of blood flow in the brain at the time the oxygen was delivered, and the new study indicates that the timing of the delivery of 100 percent oxygen is critical to achieving the benefit.

Stroke is the third-leading cause of death in the United States, and an effective treatment remains elusive. So-called "clot-busting" drugs dissolve the clots, but typically must be administered within three hours of the stroke's onset. The average time between the start of a stroke and a patient's arrival at a hospital is about four hours.

The researchers tested the effects of supplemental oxygen therapy on five groups of rats in which the scientists induced a 90-minute ischemic stroke and then restored blood flow in the animals' brains. An ischemic stroke means a clot is blocking blood flow in the brain, rather than hemorrhagic, strokes that occur when blood vessels rupture in the brain.

Two groups of animals received either normal oxygen or pressurized oxygen while blood flow was blocked in the brain. Two other sets of rats received normal or pressurized oxygen after blood flow was restored. A control group received no supplemental oxygen, breathing room air instead.

Two days later, the researchers examined the rats' brains using powerful 4.7-Tesla magnetic resonance imaging to calculate the volume of damaged tissue. The images showed the size of the infarct, or the area of tissue susceptible to stroke damage as a result of poor oxygenation.

The images showed that the animals that received supplemental oxygen treatment while blood flow was blocked had a significantly smaller amount of tissue damage compared to the rats that received oxygen after blood flow was restored.

By further examining images of the rats' brains, the scientists determined that the supplemental oxygen during the active period of a stroke specifically reduced the death of neurons and prevented the damage that free radicals can cause to lipids that help protect those brain cells. By comparison, more dead neurons and oxidative stress were found in the brains of rats receiving oxygen only after blood flow was restored.

"Ultimately, the supplemental oxygen after blood flow is restored is more than the tissue can handle, and is more than it needs. Why add oxygen on top of tissue that's already oxygenated?" said Cameron Rink, a co-investigator on the research. "Supplemental oxygen during the blockage, on the other hand, is highly protective."

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References:
1. Savita Khanna, et al. Ohio State University.

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