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Behavioral alterations following blood-brain barrier disruption stimulated by focused ultrasound.

Authors: Yang FY, Huang SF, Cheng IH

The purpose of this study was to investigate the behavioral alterations and histological changes of the brain after FUS-induced BBB disruption (BBBD). Rats were behaviorally tested using the open field, hole-board, and grip strength tests from day 1 through day 32 after undergoing BBBD induced by FUS with either a mild or heavy parameter. In the open field test, we found an increase in center entries on day 1 and day 9 following heavy FUS treatment and a decrease in center entries at day 18 following mild FUS treatment. With regard to memory-related alterations, rats subjected to heavy FUS treatment exhibited longer latency to start exploring and to find the first baited hole. However, rats subjected to mild FUS treatment exhibited no significant differences in terms of memory performance or grip force. The obtained data suggest that heavy FUS treatment might induce hyperactivity, spatial memory impairment, and forelimb gripping deficits. Furthermore, while mild FUS treatment may have an impact on anxiety-related behaviors, the data suggested it had no impact on locomotor activity, memory, or grip force. Thus, the behavioral alterations following FUS-induced BBBD require further investigation before clinical application.

Introduction

Purpose BBB opening without drug delivery
Study Objective To investigate behavioral alterations and brain histological changes following focused ultrasound-induced blood-brain barrier disruption in rats.
Animal model / Human subject Rat (Rattus norvegicus); strain: None; age: None; sex: None
Disease model Healthy

Outcomes and Safety

Summary of Outcomes Heavy FUS-induced BBB disruption produced hyperactivity and habituation deficits, spatial memory impairment, reduced forelimb grip strength, and increased hippocampal/cortical apoptosis and hemorrhage; mild FUS produced only transient anxiety-related behavior with minimal effects on locomotion, memory, or grip. Tested parameters: two FUS settings (heavy and mild) — heavy caused pronounced behavioral and histological damage, mild caused limited/anxiety-like effects.
Duration of biological effect 32 days
Safety-related matter Heavy FUS-induced BBBD produced adverse behavioral and histological effects including hyperactivity, habituation deficit, impaired spatial memory, reduced forelimb grip strength, increased hippocampal/cortical apoptosis and acute red blood cell extravasation (hemorrhage), although BBB integrity appeared re-established by 24 h; mild FUS produced anxiety-like behavior, transient TUNEL-positive cells on day 1 and a body-weight decrease by day 32 but showed no significant deficits in locomotor activity, memory or grip force.

Brain Region

Visualization unavailable

Ultrasound Parameters

Focal Characteristics Focal depth: None; Focal length: None; Aperture size: None
Treatment frequency single

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