Choi, Hyo Jin Han, Mun Jung, Byeongjin Hong, Yu-Ri Shin, Seulgi Lim, Sungsu Lee, Eun-Hee Kim, Yun Kyung Park, Juyoung 2024-01-19T10:32:20Z 2024-01-19T10:32:20Z 2023-01-19 2022-12 https://pubs.kist.re.kr/handle/201004/114209 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-beta (A beta) 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 A beta plaques. This study revealed the potential of FUS-BBBD as an effective strategy to enhance the efficacy of therapeutic drugs for AD. English MDPI AG Methylene Blue Delivery Mediated by Focused Ultrasound-Induced Blood-Brain Barrier Disruption Reduces Neural Damage and Amyloid-Beta Plaques by AQP-4 Upregulation Article 10.3390/biomedicines10123191 1 Biomedicines, v.10, no.12 Biomedicines 10 12 Y scie scopus 000902300700001 2-s2.0-85144975449 Biochemistry & Molecular Biology Medicine, Research & Experimental Pharmacology & Pharmacy Biochemistry & Molecular Biology Research & Experimental Medicine Pharmacology & Pharmacy Article CEREBROSPINAL-FLUID INTERSTITIAL FLUID DISEASE CLEARANCE DRUG FACILITATION AQUAPORIN-4 EXCHANGE MRI DIAGNOSIS blood-brain barrier focused ultrasound methylene blue Alzheimer&apos s disease aquaporin-4