The blood-brain barrier plays an important role in protecting the human brain from harmful toxins. But it also stops potentially helpful drugs from reaching the brain. Now, researchers believe that tiny bubbles loaded with drugs and delivered using ultrasound could overcome the obstacles presented by the protective network of vessels.
Researchers at the University of Oxford and the University of Twente have developed an in vitro experimental platform that they believe could aid investigations into the way the blood-brain barrier opens, how long it takes to close again and the sounds given off as it opens.
“The key advantage of our system is that it uses three modalities — involving light, sound, and electrical fields — to simultaneously monitor acoustic emissions, blood-brain barrier disruption and recovery, and the biological response of blood-brain barrier cells in real-time,” Miles Aron, from the University of Oxford, said in prepared remarks.
Using ultrasound to open the blood-brain barrier is not a new idea – researchers have been trying to do it since the 1950s.
There are a number of cavitation agents, like tiny bubbles, approved by the FDA to boost contrast in ultrasound imaging. These agents oscillate rapidly when exposed to ultrasound, helping to open the blood-brain barrier.
“The treatment can be monitored externally by ‘listening’ to the re-radiated sound from the cavitation agents interacting with the ultrasound field. These acoustic emissions provide information regarding the energy of cavitation within the blood vessels and are already being used to adjust ultrasound parameters in real-time to reduce the likelihood of damaging healthy cells during treatment,” Aron said.
The team monitored the integrity of the barrier, as well as acoustic emissions, in real-time throughout treatment. Traditionally, researchers can only assess how well a delivery method penetrated the blood-brain barrier after a treatment is finished.
The team also used fluorescent probes to assess changes in the cells throughout treatment.
“By analyzing multiple sources of data during ultrasound exposure and throughout BBB recovery, we aim to better understand this promising new treatment,” Aron said. “With the Oxford Centre for Drug Delivery Devices, OxCD3, we are currently working on a non-invasive method to detect and treat brain metastases before they become deadly. Our in vitro system will play a critical role in the development of this and other next-generation approaches to ultrasound-mediated blood brain barrier opening.”
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