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Alzheimer Disease in a Mouse Model: MR Imaging–guided Focused Ultrasound Targeted to the Hippocampus Opens the Blood-Brain Barrier and Improves Pathologic Abnormalities and Behavior
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PURPOSE: To validate whether repeated magnetic resonance (MR) imaging-guided focused ultrasound treatments targeted to the hippocampus, a brain structure relevant for Alzheimer disease ( AD Alzheimer disease ), could modulate pathologic abnormalities, plasticity, and behavior in a mouse model. MATERIALS AND METHODS: All animal procedures were approved by the Animal Care Committee and are in accordance with the Canadian Council on Animal Care. Seven-month-old transgenic (TgCRND8) (Tg) mice and their nontransgenic (non-Tg) littermates were entered in the study. Mice were treated weekly with MR imaging-guided focused ultrasound in the bilateral hippocampus (1.68 MHz, 10-msec bursts, 1-Hz burst repetition frequency, 120-second total duration). After 1 month, spatial memory was tested in the Y maze with the novel arm prior to sacrifice and immunohistochemical analysis. The data were compared by using unpaired t tests and analysis of variance with Tukey post hoc analysis. RESULTS: Untreated Tg mice spent 61% less time than untreated non-Tg mice exploring the novel arm of the Y maze because of spatial memory impairments (P < .05). Following MR imaging-guided focused ultrasound, Tg mice spent 99% more time exploring the novel arm, performing as well as their non-Tg littermates. Changes in behavior were correlated with a reduction of the number and size of amyloid plaques in the MR imaging-guided focused ultrasound-treated animals (P < .01). Further, after MR imaging-guided focused ultrasound treatment, there was a 250% increase in the number of newborn neurons in the hippocampus (P < .01). The newborn neurons had longer dendrites and more arborization after MR imaging-guided focused ultrasound, as well (P < .01). CONCLUSION: Repeated MR imaging-guided focused ultrasound treatments led to spatial memory improvement in a Tg mouse model of AD Alzheimer disease . The behavior changes may be mediated by decreased amyloid pathologic abnormalities and increased neuronal plasticity.
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“A magnetic resonance guide can be a good solution to focus ultrasound in combination with intravenously injected microbubbles in order to transiently open the BBB and reduce Aβ and τau pathology in animal models of AD [258].”
From Alzheimer's Disease: Treatment Strategies and Their Limitations. (2022) · cites this paper as [258]
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“Animal studies have demonstrated safe and reversible BBB opening (4, 6, 7) as well as reduction of amyloid-beta plaque, neurogenesis, and improvement of memory.”
From Noninvasive hippocampal blood-brain barrier opening in Alzheimer's disease with focused ultrasound. (2020) · cites this paper as [6]
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“Animal studies have demonstrated safe and reversible BBB opening (4, 6, 7) as well as reduction of amyloid-beta plaque, neurogenesis, and improvement of memory.”
From Noninvasive hippocampal blood-brain barrier opening in Alzheimer's disease with focused ultrasound. (2020) · cites this paper as [6]
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- Burgess, A., Dubey, S., Yeung, S., Hough, O., Eterman, N., Aubert, I., & Hynynen, K.
- Affiliations
- University of Toronto (CA)
- Sunnybrook Research Institute (CA)
- Venue
- Radiology
- Published
- 2014-12
- Volume
- 273
- Issue
- 3
- Pages
- 736-745
- ISSN
- 0033-8419 (ISSN-L)
- 1527-1315
- PMC
- PMC4314115
- OpenAlex
- W2131358222
- Cited by
- 286
- References
- 31
- Citations by year
- 2026: 14 · 2025: 18 · 2024: 19 · 2023: 24 · 2022: 29 · 2021: 41 · 2020: 34 · 2019: 26 · 2018: 31 · 2017: 17 · 2016: 19 · 2015: 10 · 2014: 3
- FWCI
- 8.48
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Radiology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (FRN 119312, EB003268)
- Canadian Institutes of Health Research (R01 EB003268, FRN93063, 119312_1)
- National Institute of Biomedical Imaging and Bioengineering (R01EB003268)
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › Ultrasound and Hyperthermia Applications
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Keywords
- Alzheimer's disease, hippocampus, blood-brain barrier opening, TgCRND8 mice, amyloid plaques, spatial memory, newborn neurons, neuroplasticity, dendritic branching, transgenic mouse model
- MeSH terms
- Algorithms, Alzheimer Disease, Animals, Blood-Brain Barrier, Contrast Media, Disease Models, Animal, Fluorocarbons, Hippocampus, Mice, Transgenic, Ultrasonic Therapy, Gadolinium DTPA, Mice, Magnetic Resonance Imaging, Interventional
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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