Ultrasound may boost survival after a stroke by clearing brain debris

Pulsing ultrasound waves through the brain may improve survival after stroke by helping clear inflamed dead blood cells, according to a study in mice. An approach that enhances the effect of lymphatic drainage may also help treat Alzheimer's disease. Trials in people with the disease are expected to begin next year.

Hemorrhagic strokes, which account for about 15 percent of all strokesoccur when a blood vessel in the brain ruptures, causing bleeding that cuts off the oxygen supply to the brain and damages brain cells, often leading to problems with movement and cognitive abilities.

Treatment often involves sealing the damaged vessel with a small metal clamp and then removing dead red blood cells (for example, through a catheter), which would otherwise increase inflammation and cause further tissue damage. But it's a highly invasive technique that itself can lead to brain damage and infections, he says. Raag Ayran at Stanford University in California.

Ayran began to think about the potential of ultrasound pulsed outside the head after accidentally leaving such a device on for too long while using it to activate drugs in the brains of mice. “What I saw was that the spots of the drug that I injected into the brain seemed to be smeared, as if they were carried further down the brain into [cerebrospinal] a fluid that normally clears debris from the brain,” he says. “So I thought, 'Can we really use ultrasound to push the junk out of the brain?'

To investigate this, his team collected blood from the tails of mice and injected it into their brains, simulating a hemorrhagic stroke. Over the next three days, the researchers passed ultrasound waves through the skulls of half the mice for 10 minutes daily. The remaining animals did not receive treatment.

All mice then underwent a three-minute test in which they were placed in a tank with four corners, allowing them to turn left or right. Healthy mice that have no movement or cognitive problems typically turn in opposite directions 50% of the time.

The researchers found that mice in the ultrasound group turned to the left 39 percent of the time, compared to 27 percent of the time in the control group. They also found that former mice were able to cling to the metal rod more strongly than control mice. This suggests that treated animals had less brain damage, which the team later confirmed by analyzing sections of their brains after euthanasia.

A week after their brains were injected with blood, about half the mice in the control group had died, compared with a fifth of the mice in the ultrasound group. “We increased survival rates by about 30 [percentage points] in just three 10-minute ultrasound sessions,” says Airan.

Further analysis showed that the ultrasound pulses activated pressure-sensitive proteins on the animals' microglia, immune cells in the brain, making them less inflammatory and increasing their ability to absorb and clear out dead red blood cells. The pulses also increased the flow of cerebrospinal fluid through the brain, improving the clearance of dead cells from the lymph nodes in the neck. As part of the lymphatic system, they help eliminate metabolic waste from the brain.

Although further research is needed, this approach could treat other brain diseases. “If ultrasound can help remove red blood cells, which are quite large, from the brain, it should also be able to clear toxic proteins that are much smaller, e.g. [misfolded] tau, which contribute to the development of diseases such as Parkinson's and Alzheimer's,” says Ayran.

“This is a really exciting study with huge potential for future translation because it is non-invasive,” says Kathleen Caron at the University of North Carolina at Chapel Hill. The lymphatic systems of mice and humans are very similar, she says, so the approach could work in humans too.

Ultrasonic exposure considered safeTherefore, Ayran is confident that the treatment will not have any unexpected side effects, although studies are needed to confirm this.

Researchers hope to eventually try this approach on people who have had hemorrhagic strokes, but this requires urgent treatment. Therefore, they plan to collect more data on its safety and effectiveness in people with Alzheimer's disease“This is a progressive disease, the trial of which should begin next year,” says Airan.