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Methylene Blue Delivery Mediated by Focused Ultrasound-Induced Blood–Brain Barrier Disruption Reduces Neural Damage and Amyloid-Beta Plaques by AQP-4 Upregulation

Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease worldwide, causing progressive cognitive decline, memory impairment, and neurological deficits. Methylene blue (MB), an antioxidant, has emerged as a potential drug for the treatment of AD owing to its cognitive improvement and...

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Autores principales: Choi, Hyo Jin, Han, Mun, Jung, Byeongjin, Hong, Yu-Ri, Shin, Seulgi, Lim, Sungsu, Lee, Eun-Hee, Kim, Yun Kyung, Park, Juyoung
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9776289/
https://www.ncbi.nlm.nih.gov/pubmed/36551947
http://dx.doi.org/10.3390/biomedicines10123191
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author Choi, Hyo Jin
Han, Mun
Jung, Byeongjin
Hong, Yu-Ri
Shin, Seulgi
Lim, Sungsu
Lee, Eun-Hee
Kim, Yun Kyung
Park, Juyoung
author_facet Choi, Hyo Jin
Han, Mun
Jung, Byeongjin
Hong, Yu-Ri
Shin, Seulgi
Lim, Sungsu
Lee, Eun-Hee
Kim, Yun Kyung
Park, Juyoung
author_sort Choi, Hyo Jin
collection PubMed
description Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease worldwide, causing progressive cognitive decline, memory impairment, and neurological deficits. Methylene blue (MB), an antioxidant, has emerged as a potential drug for the treatment of AD owing to its cognitive improvement and neuroprotective functions. Despite the small molecular size of MB, which can cross the BBB, the therapeutic effective dosage using a BBB-permeable delivery system in a specific brain localization remains unclear. In this study, we presented magnetic resonance–guided focused ultrasound (MRgFUS) as a delivery system to enhance BBB permeability for the effective treatment of AD. MRgFUS using two ultrasound intensities (0.25 and 0.32 MPa) was used to intravenously deliver MB to the hippocampal region. Compared with treatment with 0.25 MPa FUS, treatment with 0.32 MPa FUS significantly enhanced MB brain accumulation. Deposition of amyloid-β (Aβ) plaques and neural cell damage was significantly reduced in 0.32 MPa FUS/MB-treated APP/PS1 mice. Furthermore, aquaporin-4 expression increased significantly in the 0.32 MPa FUS and 0.32 MPa FUS/MB groups without glial fibrillary acidic protein activation. The results from this study demonstrate that FUS improved MB delivery to the brain, and FUS/MB combination treatment reduced the number of Aβ plaques. This study revealed the potential of FUS-BBBD as an effective strategy to enhance the efficacy of therapeutic drugs for AD.
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spelling pubmed-97762892022-12-23 Methylene Blue Delivery Mediated by Focused Ultrasound-Induced Blood–Brain Barrier Disruption Reduces Neural Damage and Amyloid-Beta Plaques by AQP-4 Upregulation Choi, Hyo Jin Han, Mun Jung, Byeongjin Hong, Yu-Ri Shin, Seulgi Lim, Sungsu Lee, Eun-Hee Kim, Yun Kyung Park, Juyoung Biomedicines Article Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease worldwide, causing progressive cognitive decline, memory impairment, and neurological deficits. Methylene blue (MB), an antioxidant, has emerged as a potential drug for the treatment of AD owing to its cognitive improvement and neuroprotective functions. Despite the small molecular size of MB, which can cross the BBB, the therapeutic effective dosage using a BBB-permeable delivery system in a specific brain localization remains unclear. In this study, we presented magnetic resonance–guided focused ultrasound (MRgFUS) as a delivery system to enhance BBB permeability for the effective treatment of AD. MRgFUS using two ultrasound intensities (0.25 and 0.32 MPa) was used to intravenously deliver MB to the hippocampal region. Compared with treatment with 0.25 MPa FUS, treatment with 0.32 MPa FUS significantly enhanced MB brain accumulation. Deposition of amyloid-β (Aβ) plaques and neural cell damage was significantly reduced in 0.32 MPa FUS/MB-treated APP/PS1 mice. Furthermore, aquaporin-4 expression increased significantly in the 0.32 MPa FUS and 0.32 MPa FUS/MB groups without glial fibrillary acidic protein activation. The results from this study demonstrate that FUS improved MB delivery to the brain, and FUS/MB combination treatment reduced the number of Aβ plaques. This study revealed the potential of FUS-BBBD as an effective strategy to enhance the efficacy of therapeutic drugs for AD. MDPI 2022-12-08 /pmc/articles/PMC9776289/ /pubmed/36551947 http://dx.doi.org/10.3390/biomedicines10123191 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Choi, Hyo Jin
Han, Mun
Jung, Byeongjin
Hong, Yu-Ri
Shin, Seulgi
Lim, Sungsu
Lee, Eun-Hee
Kim, Yun Kyung
Park, Juyoung
Methylene Blue Delivery Mediated by Focused Ultrasound-Induced Blood–Brain Barrier Disruption Reduces Neural Damage and Amyloid-Beta Plaques by AQP-4 Upregulation
title Methylene Blue Delivery Mediated by Focused Ultrasound-Induced Blood–Brain Barrier Disruption Reduces Neural Damage and Amyloid-Beta Plaques by AQP-4 Upregulation
title_full Methylene Blue Delivery Mediated by Focused Ultrasound-Induced Blood–Brain Barrier Disruption Reduces Neural Damage and Amyloid-Beta Plaques by AQP-4 Upregulation
title_fullStr Methylene Blue Delivery Mediated by Focused Ultrasound-Induced Blood–Brain Barrier Disruption Reduces Neural Damage and Amyloid-Beta Plaques by AQP-4 Upregulation
title_full_unstemmed Methylene Blue Delivery Mediated by Focused Ultrasound-Induced Blood–Brain Barrier Disruption Reduces Neural Damage and Amyloid-Beta Plaques by AQP-4 Upregulation
title_short Methylene Blue Delivery Mediated by Focused Ultrasound-Induced Blood–Brain Barrier Disruption Reduces Neural Damage and Amyloid-Beta Plaques by AQP-4 Upregulation
title_sort methylene blue delivery mediated by focused ultrasound-induced blood–brain barrier disruption reduces neural damage and amyloid-beta plaques by aqp-4 upregulation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9776289/
https://www.ncbi.nlm.nih.gov/pubmed/36551947
http://dx.doi.org/10.3390/biomedicines10123191
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