Applications of focused ultrasound-mediated blood-brain barrier opening

Gorick, Catherine M.; Breza, Victoria R.; Nowak, Katherine M.; Cheng, Vinton W.T.; Fisher, Delaney G.; Debski, Anna C.; Hoch, Matthew R.; Demir, Zehra E.F.; Tran, Nghi M.; Schwartz, Mark R.; Sheybani, Natasha D.; Price, Richard J.

doi:10.1016/j.addr.2022.114583

Cited by 62 publications

(34 citation statements)

References 147 publications

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“…Another technique for inducing BBB TJ disruption, focused ultrasound, is currently being assessed clinically. 179 Whether, like hyperosmotic stress, the effects of focused ultrasound will have a circadian rhythm merits investigation, particularly as focused ultrasound also downregulates BBB P-gp. 180,181 In addition, given that BBB disruption occurs in many CNS diseases and can contribute to neurological dysfunction (eg, in ischemic stroke 182 ), whether there is a circadian rhythm in disease-induced BBB disruption merits further investigation.…”

Section: Circadian Rhythms and Brain-targeted Drug Delivery (Chronoth...mentioning

confidence: 99%

Circadian Rhythms of the Blood-Brain Barrier and Drug Delivery

Kim,

Keep,

Zhang

2024

Circulation Research

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The blood-brain barrier (BBB) is a critical interface separating the central nervous system from the peripheral circulation, ensuring brain homeostasis and function. Recent research has unveiled a profound connection between the BBB and circadian rhythms, the endogenous oscillations synchronizing biological processes with the 24-hour light-dark cycle. This review explores the significance of circadian rhythms in the context of BBB functions, with an emphasis on substrate passage through the BBB. Our discussion includes efflux transporters and the molecular timing mechanisms that regulate their activities. A significant focus of this review is the potential implications of chronotherapy, leveraging our knowledge of circadian rhythms for improving drug delivery to the brain. Understanding the temporal changes in BBB can lead to optimized timing of drug administration, to enhance therapeutic efficacy for neurological disorders while reducing side effects. By elucidating the interplay between circadian rhythms and drug transport across the BBB, this review offers insights into innovative therapeutic interventions.

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Section: Circadian Rhythms and Brain-targeted Drug Delivery (Chronoth...mentioning

confidence: 99%

Circadian Rhythms of the Blood-Brain Barrier and Drug Delivery

Kim,

Keep,

Zhang

2024

Circulation Research

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“…1 ). We chose the parameters of opening based on previous studies 34,35 . Specifically, we chose 0.27 MPa of pressure, a frequency of 1.53 MHz, and a 10 ms pulse length repeated once per second for 30 s per site 36,37 .…”

Section: Resultsmentioning

confidence: 99%

Acoustically Targeted Noninvasive Gene Therapy in Large Brain Regions

Nouraein

Saenz

Mundo

et al. 2023

Preprint

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Focused Ultrasound Blood-Brain Barrier Opening (FUS-BBBO) can deliver adeno-associated viral vectors (AAVs) to treat genetic disorders of the brain. However, such disorders often affect large brain regions. Moreover, the applicability of FUS-BBBO in the treatment of brain-wide genetic disorders has not yet been evaluated. Herein, we evaluated the transduction efficiency and safety of opening up to 105 sites simultaneously. Increasing the number of targeted sites increased gene delivery efficiency at each site. We achieved transduction of up to 60% of brain cells with comparable efficiency in the majority of the brain regions. Furthermore, gene delivery with FUS-BBBO was safe even when all 105 sites were targeted simultaneously without negative effects on animal weight, neuronal loss, or astrocyte activation. To evaluate the application of multi-site FUS-BBBO for gene therapy, we used it for gene editing using the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) system. FUS-BBBO-based gene delivery also leads to a significant loss of neurons at the targeted sites. Overall, this study provides a brain-wide map of transduction efficiency and the first example of multi-site gene editing after noninvasive gene delivery with FUS-BBBO.

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“…There continues to be great interest in the use of focused ultrasound with microbubbles to transiently open the BBB for drug delivery (see [ 186 ] for a recent review) and it is being used in clinical trials. For example, Epelbaum et al [ 187 ] have developed an implantable ultrasound device that they have used to repeatedly disrupt the BBB in patients with mild Alzheimer’s disease (NCT03119961).…”

Section: Drug Deliverymentioning

confidence: 99%

A year in review: brain barriers and brain fluids research in 2022

Keep

Jones

Hamilton

et al. 2023

Fluids Barriers CNS

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This aim of this editorial is to highlight progress made in brain barrier and brain fluid research in 2022. It covers studies on the blood-brain, blood-retina and blood-CSF barriers (choroid plexus and meninges), signaling within the neurovascular unit and elements of the brain fluid systems. It further discusses how brain barriers and brain fluid systems are impacted in CNS diseases, their role in disease progression and progress being made in treating such diseases.

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Applications of focused ultrasound-mediated blood-brain barrier opening

Cited by 62 publications

References 147 publications

Circadian Rhythms of the Blood-Brain Barrier and Drug Delivery

Circadian Rhythms of the Blood-Brain Barrier and Drug Delivery

Acoustically Targeted Noninvasive Gene Therapy in Large Brain Regions

A year in review: brain barriers and brain fluids research in 2022

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