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Antidepressant effects of focused ultrasound induced blood-brain-barrier opening.

Authors: Mooney SJ, Nobrega JN, Levitt AJ, Hynynen K

In many cases, hippocampal neurogenesis appears to be a hallmark of antidepressant treatments. One novel technique for inducing this type of neurogenesis is using focused ultrasound waves, in conjunction with circulating microbubbles, to open the blood-brain-barrier. The present experiment aimed to test whether this technique has antidepressant effects in a rodent model. Rats were subjected to 1, 2 or 3 weekly treatments of magnetic resonance-guided focused ultrasound in order to open the blood-brain-barrier in the hippocampal region. Before and after treatments, animals went through modified forced swim tests. 1 week after the final treatment, animals that received 2 weekly treatments showed antidepressant-like effects on behavioural measures in comparison to untreated controls. This was not the case for animals that received 1 or 3 weekly treatments. Effects had disappeared by 5 weeks following the first ultrasound treatment. These results suggest that focused ultrasound may be used for inducing short-term antidepressant effects.

Introduction

Purpose Transcranial ultrasound stimulation
Study Objective To determine whether MR-guided focused ultrasound opening of the hippocampal blood–brain barrier produces antidepressant-like effects in a rat model.
Animal model / Human subject Rat (Rattus norvegicus); strain: Sprague Dawley; age: not specified; sex: not specified
Disease model Healthy
MRI or image guidance method Magnetic resonance-guided (MRI-guided) focused ultrasound
Targeted brain region(s) Hippocampus

Outcomes and Safety

Summary of Outcomes MR-guided focused ultrasound with circulating microbubbles to open the hippocampal BBB produced short-term antidepressant-like behavioral effects in rats, with reduced immobility in the forced swim test one week after treatment but no effect at five weeks. The effect was observed only after two weekly ultrasound treatments; one or three weekly treatments were ineffective.
Duration of biological effect 1 week
Safety-related matter No adverse effects or safety issues are reported in the paper; the text contains no mention of adverse events following the focused ultrasound treatments.

Brain Region

Ultrasound Parameters

Ultrasound instrument Custom-built 1.68 MHz focused ultrasound transducer
FUS Frequency 1.68 MHz
FUS Mode pulsed
Pulse duration 10 ms
Duration of a single FUS session 2 minutes
Focal Characteristics Focal depth: 60 mm; Focal length: None; Aperture size: None
Treatment frequency multiple

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