Project Objectives
- Develop microbubble formulations capable of encapsulating central nervous system (CNS)‑active compounds for ultrasound‑mediated delivery.
- Optimise a focused ultrasound device and protocol to safely and reliably open the blood–brain barrier.
- Compare drug diffusion achieved by ultrasound‑activated microbubbles with standard intracranial surgery.
- Assess safety, welfare impact, and therapeutic efficacy in a validated mouse model of neurodevelopmental disorder.
3Rs Impact
- Replaces invasive intracranial surgery with a non‑invasive ultrasound‑based method for CNS drug delivery.
- Reduces post‑operative pain, complications, and recovery time, significantly improving animal welfare.
- Downgrades the severity levels for many neuroscience experiments from DG2 (moderate constraint) to DG1 (slight restrainst).
- Eliminates supernumerary animals lost due to surgical failure, reducing overall animal use.
Background
Delivering drugs into the brain is one of the major challenges in neuroscience because the blood–brain barrier (BBB) prevents most therapeutic molecules from entering brain tissue. As a result, many laboratories rely on invasive intracranial surgery to administer compounds directly into specific brain regions. While effective, these procedures are lengthy, painful, and associated with complications such as inflammation, bleeding, cannula obstruction, and prolonged recovery. They also require higher‑severity classifications and extensive post‑operative care.
Microbubble‑focused ultrasound (MB‑FUS) offers a promising alternative. When circulating microbubbles are activated by targeted ultrasound, they temporarily and safely open the BBB, allowing drugs to enter the brain without surgery. This technique has been shown to be safe in rodents, non‑human primates, and even humans. The present project aims to refine CNS drug delivery by comparing MB‑FUS directly with standard intracranial surgery, assessing drug diffusion, safety, welfare outcomes, and therapeutic effects in a mouse model of schizophrenia‑related neurodevelopmental disorder.
If MB‑FUS proves as effective as surgical delivery, it could substantially reduce the severity of procedures in neuroscience research and improve animal welfare across a wide range of CNS studies.
