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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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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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. |
format | Online Article Text |
id | pubmed-9776289 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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