Focused Ultrasound Induced Blood-Brain Barrier Opening for Targeting Brain Structures and Evaluating Chemogenetic Neuromodulation

Szablowski, Jerzy O.; Harb, Manwal

doi:10.3791/61352

Cited by 8 publications

(5 citation statements)

References 14 publications

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“…FUS has been previously used both to deliver genes of interest [21,30] and to selectively excite mechanosensitive ion channels [3,4,31]. An exciting neuroengineering approach that benefits from FUS-mediated viral delivery is acoustically-targeted chemogenetics (ATAC) [32,33]. ATAC combines the spatial selectivity of FUS therapies with chemically-activated receptors (i.e., DREADDs), providing a scalable method of controlling specified networks through intravenous CNO administration.…”

Section: Discussionmentioning

confidence: 99%

Non-invasive optogenetics with ultrasound-mediated gene delivery and red-light excitation

Pouliopoulos¹,

Murillo²,

Noel³

et al. 2022

Brain Stimulation

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Section: Discussionmentioning

confidence: 99%

Non-invasive optogenetics with ultrasound-mediated gene delivery and red-light excitation

Pouliopoulos¹,

Murillo²,

Noel³

et al. 2022

Brain Stimulation

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“…Afterwards, we measured GLuc bioluminescence levels while the BBB was still intact to obtain baseline GLuc signal levels. Next, we insonated mice with FUS-BBBO using a high peak negative pressure of 0.36 MPa against 8 specific brain regions within the striatum, thalamus, midbrain, and ventral hippocampus, which was within the range of pressures used for BBB opening in our previous studies 24,[28][29][30] . Lastly, we collected a blood sample after 7.5 min, which is the shortest time feasible for blood collection.…”

Section: Resultsmentioning

confidence: 99%

Acoustically-Targeted Measurement of Transgene Expression in the Brain

Seo

Trippett

Huang

et al. 2023

Preprint

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Gene expression is a critical component of brain physiology and activity, but monitoring this expression in the living brain represents a significant challenge. Here, we introduce a new paradigm called Recovery of Markers through InSonation (REMIS) for noninvasive measurement of gene expression in the brain with cell-type, spatial, and temporal specificity. Our approach relies on engineered protein markers that are designed to be expressed in neurons and exit into the interstitium. By applying ultrasound to targeted brain regions, these markers are released into the bloodstream, where they can be readily detected using biochemical techniques. REMIS can noninvasively confirm gene delivery and measure endogenous signaling in specific brain sites through a simple insonation and a subsequent blood test. Using REMIS, we successfully measured chemo-genetic induction of neuronal activity in ultrasound-targeted brain regions. REMIS recovery of markers is reliable and demonstrated improved recovery of markers from the brain into the blood in every tested animal. Overall, our work establishes a noninvasive, spatially-specific means of monitoring gene delivery outcomes and endogenous signaling in mammalian brains, opening up possibilities for brain research and noninvasive monitoring of gene therapies in the brain.

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“…In addition, non-ablative applications of MRgFUS are being explored with low-intensity FUS, such as transient neuromodulation [82][83][84] and selective opening of the blood-brain barrier (BBB) to allow for targeted pharmacotherapy to brain structures (e.g. substantia nigra, striatum in PD) [85,86].…”

Section: Discussionmentioning

confidence: 99%