The DOI matches its Crossref record; 31 of the 31 references it cites were found in a registry or an index.
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
Open accessAbstract
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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Fiji: an open-source platform for biological-image analysis
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Forecasting the global burden of Alzheimer's disease
Brookmeyer, R., Johnson, E., Ziegler‐Graham, K., & Arrighi, H. M. (2007) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2007.04.381 · Cited by 3,370
Noninvasive MR Imaging–guided Focal Opening of the Blood-Brain Barrier in Rabbits
Hynynen, K., McDannold, N. J., Vykhodtseva, N. I., & Jolesz, F. A. (2001) · Radiology · doi:10.1148/radiol.2202001804 · Cited by 1,463
Self-citationAβ peptide immunization reduces behavioural impairment and plaques in a model of Alzheimer's disease
Janus, C., Pearson, J., McLaurin, J., Mathews, P. M., Jiang, Y., Schmidt, S. D., Chishti, M. A., Horne, P., Heslin, D., French, J., et al. (2000) · Nature · doi:10.1038/35050110 · Cited by 1,431
Soluble oligomers of the amyloid β-protein impair synaptic plasticity and behavior
Selkoe, D. J. (2008) · Behavioural Brain Research · doi:10.1016/j.bbr.2008.02.016 · Cited by 1,038
Transcranial Pulsed Ultrasound Stimulates Intact Brain Circuits
Tufail, Y., Matyushov, A. D., Baldwin, N. G., Tauchmann, M. L., Georges, J., Yoshihiro, A., Tillery, S. I. H., & Tyler, W. J. (2010) · Neuron · doi:10.1016/j.neuron.2010.05.008 · Cited by 958
Chishti, M. A., Yang, D.-S., Janus, C., Phinney, A. L., Horne, P., Pearson, J., Strome, R., Zuker, N., Loukides, J., French, J., et al. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m100710200 · Cited by 955
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Self-citationSheikov, N. A., McDannold, N. J., Vykhodtseva, N. I., Jolesz, F. A., & Hynynen, K. (2004) · Ultrasound in Medicine & Biology · doi:10.1016/j.ultrasmedbio.2004.04.010 · Cited by 619
Self-citationMcDannold, N. J., Arvanitis, C., Vykhodtseva, N. I., & Livingstone, M. S. (2012) · Cancer Research · doi:10.1158/0008-5472.can-12-0128 · Cited by 600
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Blood-brain barrier opening in Alzheimer’s disease using MR-guided focused ultrasound
Lipsman, N., Meng, Y., Bethune, A. J., Huang, Y., Lam, B., Masellis, M., Herrmann, N., Heyn, C., Aubert, I., Boutet, A., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-04529-6 · Cited by 950
Self-citationThe blood-brain barrier: Physiology and strategies for drug delivery
Pandit, R., Chen, L., & Götz, J. (2020) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2019.11.009 · Cited by 651
Alzheimer's Disease: Treatment Strategies and Their Limitations.
Passeri, E., Elkhoury, K., Morsink, M., Broersen, K., Linder, M., Tamayol, A., Malaplate, C., Yen, F. T., & Arab-Tehrany, E. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232213954 · Cited by 689
“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].”
BackgroundApplications of focused ultrasound in the brain: from thermoablation to drug delivery
Meng, Y., Hynynen, K., & Lipsman, N. (2020) · Nature Reviews Neurology · doi:10.1038/s41582-020-00418-z · Cited by 528
Self-citationDisrupting the blood–brain barrier by focused ultrasound induces sterile inflammation
Kovacs, Z. I., Kim, S., Jikaria, N., Qureshi, F., Milo, B., Lewis, B. K., Bresler, M., Burks, S. R., & Frank, J. A. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1614777114 · Cited by 458
Metadata
- Authors
- 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
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