Project Objectives
- Develop microbubbles that can carry drugs acting on the brain and release them when triggered by ultrasound.
- Set up an ultrasound device and protocol that opens the blood-brain barrier safely and reliably.
- Compare how far the drug spreads using this method against delivery by conventional brain surgery.
- Assess the safety, the welfare impact and the therapeutic effect in an established mouse model of a neurodevelopmental disorder.
3Rs Impact
- Replaces invasive brain surgery with a method that requires no incision, avoiding post-operative pain, complications and recovery time.
- Lowers the severity classification of many neuroscience experiments, from moderate to mild.
- Removes the animals currently lost when surgery fails, which are additional to those the experiment itself needs.
- If it works as well as surgery, the same approach applies across a wide range of studies that deliver drugs to the brain.
Background
The blood-brain barrier is the lining of the brain’s blood vessels, and it keeps most substances in the bloodstream out of brain tissue. It is one of the central difficulties in neuroscience: a drug that works on brain cells in a dish may never reach them in a living animal.
The usual way around it is surgery. A cannula is implanted through the skull so that drugs can be delivered straight to the target region. It works, but the operations are long and painful, and they bring complications including inflammation, bleeding, blocked cannulas and slow recovery. They also require a higher severity classification and considerable post-operative care.
There is an alternative. Microbubbles, small gas-filled spheres, can be injected into the bloodstream and then hit with focused ultrasound aimed at one part of the brain. The bubbles oscillate, which briefly loosens the barrier at that spot and lets a drug cross. The opening closes again afterwards. The technique has been shown to be safe in rodents, in non-human primates and in people.
This project compared the two directly in a mouse model related to schizophrenia, measuring how far the drug spread, whether the method was safe, what it meant for the animals’ welfare, and whether the treatment worked.
