The blood-brain barrier is a protective layer that surrounds the brain. Its main function is to prevent potentially harmful agents from leaking into this organ. However, it can also stop certain therapeutic drugs from reaching their target. The blood-brain barrier prevents antitumor drugs and those that fight the symptoms of neurological conditions such as Alzheimer's disease from reaching the brain and doing their work.

Scientists can address this issue by temporarily bypassing the blood-brain barrier using low-frequency ultrasound pulses. So far, they have only experimented with long-wave ultrasound pulses. However, these can bring on side effects, such as brain tissue damage and prolonged exposure to harmful molecules penetrating the blood-brain barrier alongside the drugs.

Now, research conducted at Imperial College London in the United Kingdom suggests that a new approach to ultrasound disruption of the blood-brain barrier may work better and cause fewer problems. The team—led by James Choi, PhD—is focusing on the use of shorter-wave ultrasound pulses, which the scientists have recently tested in mouse models.

Following the new research, the results of which appear in the journal Radiology, Choi notes that he and his colleagues "have now found a seemingly effective way of getting potentially effective drugs to where they need to be."

'Literally opening up the brain' to treatments

In the new study, the scientists compared the effects of long- and short-wave ultrasound pulses in the disruption of the blood-brain barrier in mouse models.

They injected the 28 rodents with microbubbles that can carry specific drugs to their target. Then, they applied long-wave ultrasounds to 14 of these mice and short-wave ultrasounds to the remaining 14. The pulses modify the pressure within blood vessels, which allows the microbubbles to expand or contract, which, in turn, helps them penetrate the blood-brain barrier little by little.

Choi and team revealed that using short-wave pulses led to effective drug delivery to the brain without causing tissue damage. This is one of the side effects of long-wave pulses. Also, they saw that the blood-brain barrier closed down again within 10 minutes of the short-wave pulse intervention, which means that pathogens had less of a chance to leak into the brain.

"The blood-brain barrier," says Choi, "is relatively simple to open but current techniques are unable to do so safely—which is why we haven't been able to use them in humans without side effects. Our new way of applying the ultrasound could, following further research, literally open up the brain to all sorts of drugs we had previously disregarded."

Their study, the scientists add, received funding from Alzheimer's Research UK, a registered charity that supports research into treatments for Alzheimer's and other forms of dementia. This was because they harbor a hope that their new method of delivering treatments straight to the brain may be helpful in the context of therapies for Alzheimer's, other neurological conditions, and brain cancers.

"Many potential drugs that looked promising in laboratory settings," says Choi, "never moved on to use in people—possibly because they were blocked by the blood-brain barrier when it came to using them in humans," Choi says.

"While the blood-brain barrier protects the brain against damage and infection, it does make it very difficult to deliver treatments into the brain," adds Dr. Sara Imarisio, who is head of research at Alzheimer's Research UK and did not participate in the new study.

She concludes, "Although this study exploring how we can penetrate the blood-brain barrier was conducted in mice, it's a critical step before technology like this can be tested in people."