Focused Ultrasound-Induced Neurogenesis Requires an Increase in Blood-Brain Barrier Permeability

Area of Science:

• Neuroscience
• Biomedical Engineering

Background:

• Transcranial focused ultrasound (tFUS) can open the blood-brain barrier (BBB) and stimulate hippocampal neurogenesis.
• The specific parameters of tFUS required for enhanced neurogenesis are not fully understood.

Purpose of the Study:

• To investigate whether BBB opening, specific focused ultrasound pressure amplitudes, or microbubble administration are necessary for enhanced neurogenesis.
• To determine the optimal conditions for focused ultrasound-mediated neurogenesis.

Main Methods:

• Mice were exposed to burst focused ultrasound (1.68MHz, 10ms duration, 1Hz repetition frequency) at various pressure amplitudes (0.39–3.0MPa).
• Treatments were administered with or without intravenous microbubbles (phospholipid microspheres).
• Hippocampal neurogenesis and BBB permeability were assessed.

Main Results:

• Focused ultrasound at approximately 0.78MPa pressure amplitude, in combination with microbubbles, significantly promoted hippocampal neurogenesis.
• This combination was also associated with a measurable increase in blood-brain barrier permeability.
• Other tested parameters, including higher pressure amplitudes or ultrasound without microbubbles, did not yield similar results.

Conclusions:

• Focused ultrasound-mediated enhancement of hippocampal neurogenesis is dependent on the transient opening of the blood-brain barrier.
• The combination of specific focused ultrasound parameters and microbubble administration is crucial for this effect.